The goal of geroscience is life extension
Oncotarget. 2021 Feb 2;12(3):131-144. doi: 10.18632/oncotarget.27882. eCollection 2021 Feb 2.ABSTRACTAlthough numerous drugs seemingly extend healthspan in mice, only a few extend lifespan in mice and only one does it consistently. Some of them, alone or in combination, can be used in humans, without further clinical trials.PMID:33613842 | PMC:PMC7869575 | DOI:10.18632/oncotarget.27882 (Source: Oncotarget)
Source: Oncotarget - February 22, 2021 Category: Cancer & Oncology Authors: Mikhail V Blagosklonny Source Type: research

Downregulation of SOX2 by inhibition of Usp9X induces apoptosis in melanoma
Oncotarget. 2021 Feb 2;12(3):160-172. doi: 10.18632/oncotarget.27869. eCollection 2021 Feb 2.ABSTRACTMelanoma tumors driven by BRAF mutations often do not respond to BRAF/MEK/ERK pathway inhibitors currently used in treatment. One documented mechanism of resistance is upregulation of SOX2, a transcription factor that is essential for tumor growth and expansion, particularly in melanoma tumors with BRAF mutations. Targeting transcription factors pharmacologically has been elusive for drug developers, limiting treatment options. Here we show that ubiquitin-specific peptidase 9, X-linked (Usp9x), a deubiquitinase (DUB) enzyme...
Source: Oncotarget - February 22, 2021 Category: Cancer & Oncology Authors: Harish Potu Malathi Kandarpa Luke F Peterson Alison Durham Nicholas J Donato Moshe Talpaz Source Type: research

MicroRNA-214 enriched exosomes from human cerebral endothelial cells (hCEC) sensitize hepatocellular carcinoma to anti-cancer drugs
In conclusion, the present in vitro study provides evidence that hCEC-Exo-214 significantly enhances the anti-tumor efficacy of oxaliplatin and sorafenib on HCC cells.PMID:33613846 | PMC:PMC7869574 | DOI:10.18632/oncotarget.27879 (Source: Oncotarget)
Source: Oncotarget - February 22, 2021 Category: Cancer & Oncology Authors: Louie Semaan Qingning Zeng Yong Lu Yi Zhang Mehdi Mohamad Zreik Mohamad Baqer Chamseddine Michael Chopp Zheng Gang Zhang Dilip Moonka Source Type: research

Unravelling actionable biology using transcriptomic data to integrate mitotic index and Ki-67 in the management of lung neuroendocrine tumors
In this study, we investigated the association of mitotic rate and Ki-67 at gene- and pathway-level using transcriptomic data in lung NET malignancies. Lung resection tumor specimens obtained from 28 patients diagnosed with NETs were selected. Mitotic rate, Ki-67 and transcriptomic data were obtained for all samples. The concordance between mitotic rate and Ki-67 was evaluated at gene-level and pathway-level using gene expression data. Our analysis revealed a strong association between mitotic rate and Ki-67 across all samples and cell cycle genes were found to be differentially ranked between them. Pathway analysis indica...
Source: Oncotarget - February 22, 2021 Category: Cancer & Oncology Authors: Venkata S K Manem Olga Sazonova Andr éanne Gagné Mich èle Orain Babak Khoshkrood-Mansoori Nathalie Gaudreault Yohan Boss é Philippe Joubert Source Type: research

Folinic acid in colorectal cancer: esquire or fellow knight? Real-world results from a mono institutional, retrospective study
Oncotarget. 2021 Feb 2;12(3):221-229. doi: 10.18632/oncotarget.27872. eCollection 2021 Feb 2.ABSTRACTThe stock of therapeutic weapons available in metastatic colorectal cancer (mCRC) has been progressively grown over the years, with improving both survival and patients' clinical outcome: notwithstanding advances in the knowledge of mCRC biology, as well as advances in treatment, fluoropyrimidine antimetabolite drugs have been for 30 years the mainstay of chemotherapy protocols for this malignancy. 5-Fluorouracil (5FU) seems to act differently depending on administration method: elastomer-mediated continuous infusion better...
Source: Oncotarget - February 22, 2021 Category: Cancer & Oncology Authors: Francesco Jacopo Romano Carmela Barbato Maria Biglietto Vincenzo Di Lauro Dario Arundine Roberto Fiorentino Francesca Ambrosio Maresa Cammarota Bruno Chiurazzi Livio Puglia Sarah Scagliarini Raffaella Ruocco Carmen Mocerino Ivana Cerillo Maria Fiorella Br Source Type: research

Cancer stem cells and macrophages: molecular connections and future perspectives against cancer
Oncotarget. 2021 Feb 2;12(3):230-250. doi: 10.18632/oncotarget.27870. eCollection 2021 Feb 2.ABSTRACTCancer stem cells (CSCs) have been considered the key drivers of cancer initiation and progression due to their unlimited self-renewal capacity and their ability to induce tumor formation. Macrophages, particularly tumor-associated macrophages (TAMs), establish a tumor microenvironment to protect and induce CSCs development and dissemination. Many studies in the past decade have been performed to understand the molecular mediators of CSCs and TAMs, and several studies have elucidated the complex crosstalk that occurs betwee...
Source: Oncotarget - February 22, 2021 Category: Cancer & Oncology Authors: Beatrice Aramini Valentina Masciale Giulia Grisendi Federico Banchelli Roberto D'Amico Antonino Maiorana Uliano Morandi Massimo Dominici Khawaja Husnain Haider Source Type: research

Erratum: GSK3 is required for rapalogs to induce degradation of some oncogenic proteins and to suppress cancer cell growth
Oncotarget. 2021 Feb 2;12(3):251-252. doi: 10.18632/oncotarget.27752. eCollection 2021 Feb 2.ABSTRACT[This corrects the article DOI: 10.18632/oncotarget.3291.].PMID:33613851 | PMC:PMC7869579 | DOI:10.18632/oncotarget.27752 (Source: Oncotarget)
Source: Oncotarget - February 22, 2021 Category: Cancer & Oncology Authors: Junghui Koo Xuerong Wang Taofeek K Owonikoko Suresh S Ramalingam Fadlo R Khuri Shi-Yong Sun Source Type: research

High mRNA expression of LY6 gene family is associated with overall survival outcome in pancreatic ductal adenocarcinoma
Oncotarget. 2021 Feb 2;12(3):145-159. doi: 10.18632/oncotarget.27880. eCollection 2021 Feb 2.ABSTRACTPancreatic cancer ranks one of the worst in overall survival outcome with a 5 year survival rate being less than 10%. Pancreatic cancer faces unique challenges in its diagnosis and treatment, such as the lack of clinically validated biomarkers and the immensely immunosuppressive tumor microenvironment. Recently, the LY6 gene family has received increasing attention for its multi-faceted roles in cancer development, stem cell maintenance, immunomodulation, and association with more aggressive and hard-to-treat cancers. A det...
Source: Oncotarget - February 22, 2021 Category: Cancer & Oncology Authors: Eric Russ Krithika Bhuvaneshwar Guisong Wang Benjamin Jin Michele M Gage Subha Madhavan Yuriy Gusev Geeta Upadhyay Source Type: research

A novel isoform of Homeodomain-interacting protein kinase-2 promotes YAP/TEAD transcriptional activity in NSCLC cells
In this study, we show that a new HIPK2 isoform increases TEAD reporter activity in NSCLC cells. We detected HIPK2 copy number gain in 5/6 (83.3%) NSCLC cell lines. In NSCLC patients with high HIPK2 mRNA expression in the Human Protein Atlas, the five-year survival rate is significantly lower than in patients with low expression (38% vs 47%; p = 0.047). We also found that 70/78 (89.7%) of NSCLC tissues have moderate to strong expression of the N-terminal HIPK2 protein. We detected and cloned a novel HIPK2 isoform 3 and found that its forced overexpression promotes TEAD reporter activity in NSCLC cells. Expressing HIPK2 iso...
Source: Oncotarget - February 22, 2021 Category: Cancer & Oncology Authors: Yuyuan Dai Hiroyuki Kyoyama Yi-Lin Yang Yucheng Wang Shu Liu Yinghao Wang Jian-Hua Mao Zhidong Xu Kazutsugu Uematsu David M Jablons Liang You Source Type: research

Testosterone deficiency in men receiving immunotherapy for malignant melanoma
Oncotarget. 2021 Feb 2;12(3):199-208. doi: 10.18632/oncotarget.27876. eCollection 2021 Feb 2.ABSTRACTImmunotherapy has been established as a standard of care for patients with malignant melanoma, however, the long-term side-effects of immunotherapy are still emerging. Studies over the last decade have documented increasing reports of endocrine dysfunction following the initiation of immunotherapy. Our study aimed to detect the proportion of men who have low testosterone before, during, and or/after receiving immunotherapy for malignant melanoma, and to determine the proportion of men who receive testosterone replacement th...
Source: Oncotarget - February 22, 2021 Category: Cancer & Oncology Authors: Madeline Peters Amy Pearlman William Terry Sarah L Mott Varun Monga Source Type: research

The goal of geroscience is life extension
Oncotarget. 2021 Feb 2;12(3):131-144. doi: 10.18632/oncotarget.27882. eCollection 2021 Feb 2.ABSTRACTAlthough numerous drugs seemingly extend healthspan in mice, only a few extend lifespan in mice and only one does it consistently. Some of them, alone or in combination, can be used in humans, without further clinical trials.PMID:33613842 | PMC:PMC7869575 | DOI:10.18632/oncotarget.27882 (Source: Oncotarget)
Source: Oncotarget - February 22, 2021 Category: Cancer & Oncology Authors: Mikhail V Blagosklonny Source Type: research

Downregulation of SOX2 by inhibition of Usp9X induces apoptosis in melanoma
Oncotarget. 2021 Feb 2;12(3):160-172. doi: 10.18632/oncotarget.27869. eCollection 2021 Feb 2.ABSTRACTMelanoma tumors driven by BRAF mutations often do not respond to BRAF/MEK/ERK pathway inhibitors currently used in treatment. One documented mechanism of resistance is upregulation of SOX2, a transcription factor that is essential for tumor growth and expansion, particularly in melanoma tumors with BRAF mutations. Targeting transcription factors pharmacologically has been elusive for drug developers, limiting treatment options. Here we show that ubiquitin-specific peptidase 9, X-linked (Usp9x), a deubiquitinase (DUB) enzyme...
Source: Oncotarget - February 22, 2021 Category: Cancer & Oncology Authors: Harish Potu Malathi Kandarpa Luke F Peterson Alison Durham Nicholas J Donato Moshe Talpaz Source Type: research

MicroRNA-214 enriched exosomes from human cerebral endothelial cells (hCEC) sensitize hepatocellular carcinoma to anti-cancer drugs
In conclusion, the present in vitro study provides evidence that hCEC-Exo-214 significantly enhances the anti-tumor efficacy of oxaliplatin and sorafenib on HCC cells.PMID:33613846 | PMC:PMC7869574 | DOI:10.18632/oncotarget.27879 (Source: Oncotarget)
Source: Oncotarget - February 22, 2021 Category: Cancer & Oncology Authors: Louie Semaan Qingning Zeng Yong Lu Yi Zhang Mehdi Mohamad Zreik Mohamad Baqer Chamseddine Michael Chopp Zheng Gang Zhang Dilip Moonka Source Type: research

Unravelling actionable biology using transcriptomic data to integrate mitotic index and Ki-67 in the management of lung neuroendocrine tumors
In this study, we investigated the association of mitotic rate and Ki-67 at gene- and pathway-level using transcriptomic data in lung NET malignancies. Lung resection tumor specimens obtained from 28 patients diagnosed with NETs were selected. Mitotic rate, Ki-67 and transcriptomic data were obtained for all samples. The concordance between mitotic rate and Ki-67 was evaluated at gene-level and pathway-level using gene expression data. Our analysis revealed a strong association between mitotic rate and Ki-67 across all samples and cell cycle genes were found to be differentially ranked between them. Pathway analysis indica...
Source: Oncotarget - February 22, 2021 Category: Cancer & Oncology Authors: Venkata S K Manem Olga Sazonova Andr éanne Gagné Mich èle Orain Babak Khoshkrood-Mansoori Nathalie Gaudreault Yohan Boss é Philippe Joubert Source Type: research

Folinic acid in colorectal cancer: esquire or fellow knight? Real-world results from a mono institutional, retrospective study
Oncotarget. 2021 Feb 2;12(3):221-229. doi: 10.18632/oncotarget.27872. eCollection 2021 Feb 2.ABSTRACTThe stock of therapeutic weapons available in metastatic colorectal cancer (mCRC) has been progressively grown over the years, with improving both survival and patients' clinical outcome: notwithstanding advances in the knowledge of mCRC biology, as well as advances in treatment, fluoropyrimidine antimetabolite drugs have been for 30 years the mainstay of chemotherapy protocols for this malignancy. 5-Fluorouracil (5FU) seems to act differently depending on administration method: elastomer-mediated continuous infusion better...
Source: Oncotarget - February 22, 2021 Category: Cancer & Oncology Authors: Francesco Jacopo Romano Carmela Barbato Maria Biglietto Vincenzo Di Lauro Dario Arundine Roberto Fiorentino Francesca Ambrosio Maresa Cammarota Bruno Chiurazzi Livio Puglia Sarah Scagliarini Raffaella Ruocco Carmen Mocerino Ivana Cerillo Maria Fiorella Br Source Type: research

Cancer stem cells and macrophages: molecular connections and future perspectives against cancer
Oncotarget. 2021 Feb 2;12(3):230-250. doi: 10.18632/oncotarget.27870. eCollection 2021 Feb 2.ABSTRACTCancer stem cells (CSCs) have been considered the key drivers of cancer initiation and progression due to their unlimited self-renewal capacity and their ability to induce tumor formation. Macrophages, particularly tumor-associated macrophages (TAMs), establish a tumor microenvironment to protect and induce CSCs development and dissemination. Many studies in the past decade have been performed to understand the molecular mediators of CSCs and TAMs, and several studies have elucidated the complex crosstalk that occurs betwee...
Source: Oncotarget - February 22, 2021 Category: Cancer & Oncology Authors: Beatrice Aramini Valentina Masciale Giulia Grisendi Federico Banchelli Roberto D'Amico Antonino Maiorana Uliano Morandi Massimo Dominici Khawaja Husnain Haider Source Type: research

Erratum: GSK3 is required for rapalogs to induce degradation of some oncogenic proteins and to suppress cancer cell growth
Oncotarget. 2021 Feb 2;12(3):251-252. doi: 10.18632/oncotarget.27752. eCollection 2021 Feb 2.ABSTRACT[This corrects the article DOI: 10.18632/oncotarget.3291.].PMID:33613851 | PMC:PMC7869579 | DOI:10.18632/oncotarget.27752 (Source: Oncotarget)
Source: Oncotarget - February 22, 2021 Category: Cancer & Oncology Authors: Junghui Koo Xuerong Wang Taofeek K Owonikoko Suresh S Ramalingam Fadlo R Khuri Shi-Yong Sun Source Type: research

High mRNA expression of LY6 gene family is associated with overall survival outcome in pancreatic ductal adenocarcinoma
Oncotarget. 2021 Feb 2;12(3):145-159. doi: 10.18632/oncotarget.27880. eCollection 2021 Feb 2.ABSTRACTPancreatic cancer ranks one of the worst in overall survival outcome with a 5 year survival rate being less than 10%. Pancreatic cancer faces unique challenges in its diagnosis and treatment, such as the lack of clinically validated biomarkers and the immensely immunosuppressive tumor microenvironment. Recently, the LY6 gene family has received increasing attention for its multi-faceted roles in cancer development, stem cell maintenance, immunomodulation, and association with more aggressive and hard-to-treat cancers. A det...
Source: Oncotarget - February 22, 2021 Category: Cancer & Oncology Authors: Eric Russ Krithika Bhuvaneshwar Guisong Wang Benjamin Jin Michele M Gage Subha Madhavan Yuriy Gusev Geeta Upadhyay Source Type: research

A novel isoform of Homeodomain-interacting protein kinase-2 promotes YAP/TEAD transcriptional activity in NSCLC cells
In this study, we show that a new HIPK2 isoform increases TEAD reporter activity in NSCLC cells. We detected HIPK2 copy number gain in 5/6 (83.3%) NSCLC cell lines. In NSCLC patients with high HIPK2 mRNA expression in the Human Protein Atlas, the five-year survival rate is significantly lower than in patients with low expression (38% vs 47%; p = 0.047). We also found that 70/78 (89.7%) of NSCLC tissues have moderate to strong expression of the N-terminal HIPK2 protein. We detected and cloned a novel HIPK2 isoform 3 and found that its forced overexpression promotes TEAD reporter activity in NSCLC cells. Expressing HIPK2 iso...
Source: Oncotarget - February 22, 2021 Category: Cancer & Oncology Authors: Yuyuan Dai Hiroyuki Kyoyama Yi-Lin Yang Yucheng Wang Shu Liu Yinghao Wang Jian-Hua Mao Zhidong Xu Kazutsugu Uematsu David M Jablons Liang You Source Type: research

Testosterone deficiency in men receiving immunotherapy for malignant melanoma
Oncotarget. 2021 Feb 2;12(3):199-208. doi: 10.18632/oncotarget.27876. eCollection 2021 Feb 2.ABSTRACTImmunotherapy has been established as a standard of care for patients with malignant melanoma, however, the long-term side-effects of immunotherapy are still emerging. Studies over the last decade have documented increasing reports of endocrine dysfunction following the initiation of immunotherapy. Our study aimed to detect the proportion of men who have low testosterone before, during, and or/after receiving immunotherapy for malignant melanoma, and to determine the proportion of men who receive testosterone replacement th...
Source: Oncotarget - February 22, 2021 Category: Cancer & Oncology Authors: Madeline Peters Amy Pearlman William Terry Sarah L Mott Varun Monga Source Type: research

The goal of geroscience is life extension
Oncotarget. 2021 Feb 2;12(3):131-144. doi: 10.18632/oncotarget.27882. eCollection 2021 Feb 2.ABSTRACTAlthough numerous drugs seemingly extend healthspan in mice, only a few extend lifespan in mice and only one does it consistently. Some of them, alone or in combination, can be used in humans, without further clinical trials.PMID:33613842 | PMC:PMC7869575 | DOI:10.18632/oncotarget.27882 (Source: Oncotarget)
Source: Oncotarget - February 22, 2021 Category: Cancer & Oncology Authors: Mikhail V Blagosklonny Source Type: research

Downregulation of SOX2 by inhibition of Usp9X induces apoptosis in melanoma
Oncotarget. 2021 Feb 2;12(3):160-172. doi: 10.18632/oncotarget.27869. eCollection 2021 Feb 2.ABSTRACTMelanoma tumors driven by BRAF mutations often do not respond to BRAF/MEK/ERK pathway inhibitors currently used in treatment. One documented mechanism of resistance is upregulation of SOX2, a transcription factor that is essential for tumor growth and expansion, particularly in melanoma tumors with BRAF mutations. Targeting transcription factors pharmacologically has been elusive for drug developers, limiting treatment options. Here we show that ubiquitin-specific peptidase 9, X-linked (Usp9x), a deubiquitinase (DUB) enzyme...
Source: Oncotarget - February 22, 2021 Category: Cancer & Oncology Authors: Harish Potu Malathi Kandarpa Luke F Peterson Alison Durham Nicholas J Donato Moshe Talpaz Source Type: research

MicroRNA-214 enriched exosomes from human cerebral endothelial cells (hCEC) sensitize hepatocellular carcinoma to anti-cancer drugs
In conclusion, the present in vitro study provides evidence that hCEC-Exo-214 significantly enhances the anti-tumor efficacy of oxaliplatin and sorafenib on HCC cells.PMID:33613846 | PMC:PMC7869574 | DOI:10.18632/oncotarget.27879 (Source: Oncotarget)
Source: Oncotarget - February 22, 2021 Category: Cancer & Oncology Authors: Louie Semaan Qingning Zeng Yong Lu Yi Zhang Mehdi Mohamad Zreik Mohamad Baqer Chamseddine Michael Chopp Zheng Gang Zhang Dilip Moonka Source Type: research

Unravelling actionable biology using transcriptomic data to integrate mitotic index and Ki-67 in the management of lung neuroendocrine tumors
In this study, we investigated the association of mitotic rate and Ki-67 at gene- and pathway-level using transcriptomic data in lung NET malignancies. Lung resection tumor specimens obtained from 28 patients diagnosed with NETs were selected. Mitotic rate, Ki-67 and transcriptomic data were obtained for all samples. The concordance between mitotic rate and Ki-67 was evaluated at gene-level and pathway-level using gene expression data. Our analysis revealed a strong association between mitotic rate and Ki-67 across all samples and cell cycle genes were found to be differentially ranked between them. Pathway analysis indica...
Source: Oncotarget - February 22, 2021 Category: Cancer & Oncology Authors: Venkata S K Manem Olga Sazonova Andr éanne Gagné Mich èle Orain Babak Khoshkrood-Mansoori Nathalie Gaudreault Yohan Boss é Philippe Joubert Source Type: research

Folinic acid in colorectal cancer: esquire or fellow knight? Real-world results from a mono institutional, retrospective study
Oncotarget. 2021 Feb 2;12(3):221-229. doi: 10.18632/oncotarget.27872. eCollection 2021 Feb 2.ABSTRACTThe stock of therapeutic weapons available in metastatic colorectal cancer (mCRC) has been progressively grown over the years, with improving both survival and patients' clinical outcome: notwithstanding advances in the knowledge of mCRC biology, as well as advances in treatment, fluoropyrimidine antimetabolite drugs have been for 30 years the mainstay of chemotherapy protocols for this malignancy. 5-Fluorouracil (5FU) seems to act differently depending on administration method: elastomer-mediated continuous infusion better...
Source: Oncotarget - February 22, 2021 Category: Cancer & Oncology Authors: Francesco Jacopo Romano Carmela Barbato Maria Biglietto Vincenzo Di Lauro Dario Arundine Roberto Fiorentino Francesca Ambrosio Maresa Cammarota Bruno Chiurazzi Livio Puglia Sarah Scagliarini Raffaella Ruocco Carmen Mocerino Ivana Cerillo Maria Fiorella Br Source Type: research

Cancer stem cells and macrophages: molecular connections and future perspectives against cancer
Oncotarget. 2021 Feb 2;12(3):230-250. doi: 10.18632/oncotarget.27870. eCollection 2021 Feb 2.ABSTRACTCancer stem cells (CSCs) have been considered the key drivers of cancer initiation and progression due to their unlimited self-renewal capacity and their ability to induce tumor formation. Macrophages, particularly tumor-associated macrophages (TAMs), establish a tumor microenvironment to protect and induce CSCs development and dissemination. Many studies in the past decade have been performed to understand the molecular mediators of CSCs and TAMs, and several studies have elucidated the complex crosstalk that occurs betwee...
Source: Oncotarget - February 22, 2021 Category: Cancer & Oncology Authors: Beatrice Aramini Valentina Masciale Giulia Grisendi Federico Banchelli Roberto D'Amico Antonino Maiorana Uliano Morandi Massimo Dominici Khawaja Husnain Haider Source Type: research

Erratum: GSK3 is required for rapalogs to induce degradation of some oncogenic proteins and to suppress cancer cell growth
Oncotarget. 2021 Feb 2;12(3):251-252. doi: 10.18632/oncotarget.27752. eCollection 2021 Feb 2.ABSTRACT[This corrects the article DOI: 10.18632/oncotarget.3291.].PMID:33613851 | PMC:PMC7869579 | DOI:10.18632/oncotarget.27752 (Source: Oncotarget)
Source: Oncotarget - February 22, 2021 Category: Cancer & Oncology Authors: Junghui Koo Xuerong Wang Taofeek K Owonikoko Suresh S Ramalingam Fadlo R Khuri Shi-Yong Sun Source Type: research

High mRNA expression of LY6 gene family is associated with overall survival outcome in pancreatic ductal adenocarcinoma
Oncotarget. 2021 Feb 2;12(3):145-159. doi: 10.18632/oncotarget.27880. eCollection 2021 Feb 2.ABSTRACTPancreatic cancer ranks one of the worst in overall survival outcome with a 5 year survival rate being less than 10%. Pancreatic cancer faces unique challenges in its diagnosis and treatment, such as the lack of clinically validated biomarkers and the immensely immunosuppressive tumor microenvironment. Recently, the LY6 gene family has received increasing attention for its multi-faceted roles in cancer development, stem cell maintenance, immunomodulation, and association with more aggressive and hard-to-treat cancers. A det...
Source: Oncotarget - February 22, 2021 Category: Cancer & Oncology Authors: Eric Russ Krithika Bhuvaneshwar Guisong Wang Benjamin Jin Michele M Gage Subha Madhavan Yuriy Gusev Geeta Upadhyay Source Type: research

A novel isoform of Homeodomain-interacting protein kinase-2 promotes YAP/TEAD transcriptional activity in NSCLC cells
In this study, we show that a new HIPK2 isoform increases TEAD reporter activity in NSCLC cells. We detected HIPK2 copy number gain in 5/6 (83.3%) NSCLC cell lines. In NSCLC patients with high HIPK2 mRNA expression in the Human Protein Atlas, the five-year survival rate is significantly lower than in patients with low expression (38% vs 47%; p = 0.047). We also found that 70/78 (89.7%) of NSCLC tissues have moderate to strong expression of the N-terminal HIPK2 protein. We detected and cloned a novel HIPK2 isoform 3 and found that its forced overexpression promotes TEAD reporter activity in NSCLC cells. Expressing HIPK2 iso...
Source: Oncotarget - February 22, 2021 Category: Cancer & Oncology Authors: Yuyuan Dai Hiroyuki Kyoyama Yi-Lin Yang Yucheng Wang Shu Liu Yinghao Wang Jian-Hua Mao Zhidong Xu Kazutsugu Uematsu David M Jablons Liang You Source Type: research

Testosterone deficiency in men receiving immunotherapy for malignant melanoma
Oncotarget. 2021 Feb 2;12(3):199-208. doi: 10.18632/oncotarget.27876. eCollection 2021 Feb 2.ABSTRACTImmunotherapy has been established as a standard of care for patients with malignant melanoma, however, the long-term side-effects of immunotherapy are still emerging. Studies over the last decade have documented increasing reports of endocrine dysfunction following the initiation of immunotherapy. Our study aimed to detect the proportion of men who have low testosterone before, during, and or/after receiving immunotherapy for malignant melanoma, and to determine the proportion of men who receive testosterone replacement th...
Source: Oncotarget - February 22, 2021 Category: Cancer & Oncology Authors: Madeline Peters Amy Pearlman William Terry Sarah L Mott Varun Monga Source Type: research

The goal of geroscience is life extension
Oncotarget. 2021 Feb 2;12(3):131-144. doi: 10.18632/oncotarget.27882. eCollection 2021 Feb 2.ABSTRACTAlthough numerous drugs seemingly extend healthspan in mice, only a few extend lifespan in mice and only one does it consistently. Some of them, alone or in combination, can be used in humans, without further clinical trials.PMID:33613842 | PMC:PMC7869575 | DOI:10.18632/oncotarget.27882 (Source: Oncotarget)
Source: Oncotarget - February 22, 2021 Category: Cancer & Oncology Authors: Mikhail V Blagosklonny Source Type: research

Downregulation of SOX2 by inhibition of Usp9X induces apoptosis in melanoma
Oncotarget. 2021 Feb 2;12(3):160-172. doi: 10.18632/oncotarget.27869. eCollection 2021 Feb 2.ABSTRACTMelanoma tumors driven by BRAF mutations often do not respond to BRAF/MEK/ERK pathway inhibitors currently used in treatment. One documented mechanism of resistance is upregulation of SOX2, a transcription factor that is essential for tumor growth and expansion, particularly in melanoma tumors with BRAF mutations. Targeting transcription factors pharmacologically has been elusive for drug developers, limiting treatment options. Here we show that ubiquitin-specific peptidase 9, X-linked (Usp9x), a deubiquitinase (DUB) enzyme...
Source: Oncotarget - February 22, 2021 Category: Cancer & Oncology Authors: Harish Potu Malathi Kandarpa Luke F Peterson Alison Durham Nicholas J Donato Moshe Talpaz Source Type: research

MicroRNA-214 enriched exosomes from human cerebral endothelial cells (hCEC) sensitize hepatocellular carcinoma to anti-cancer drugs
In conclusion, the present in vitro study provides evidence that hCEC-Exo-214 significantly enhances the anti-tumor efficacy of oxaliplatin and sorafenib on HCC cells.PMID:33613846 | PMC:PMC7869574 | DOI:10.18632/oncotarget.27879 (Source: Oncotarget)
Source: Oncotarget - February 22, 2021 Category: Cancer & Oncology Authors: Louie Semaan Qingning Zeng Yong Lu Yi Zhang Mehdi Mohamad Zreik Mohamad Baqer Chamseddine Michael Chopp Zheng Gang Zhang Dilip Moonka Source Type: research

Unravelling actionable biology using transcriptomic data to integrate mitotic index and Ki-67 in the management of lung neuroendocrine tumors
In this study, we investigated the association of mitotic rate and Ki-67 at gene- and pathway-level using transcriptomic data in lung NET malignancies. Lung resection tumor specimens obtained from 28 patients diagnosed with NETs were selected. Mitotic rate, Ki-67 and transcriptomic data were obtained for all samples. The concordance between mitotic rate and Ki-67 was evaluated at gene-level and pathway-level using gene expression data. Our analysis revealed a strong association between mitotic rate and Ki-67 across all samples and cell cycle genes were found to be differentially ranked between them. Pathway analysis indica...
Source: Oncotarget - February 22, 2021 Category: Cancer & Oncology Authors: Venkata S K Manem Olga Sazonova Andr éanne Gagné Mich èle Orain Babak Khoshkrood-Mansoori Nathalie Gaudreault Yohan Boss é Philippe Joubert Source Type: research

Folinic acid in colorectal cancer: esquire or fellow knight? Real-world results from a mono institutional, retrospective study
Oncotarget. 2021 Feb 2;12(3):221-229. doi: 10.18632/oncotarget.27872. eCollection 2021 Feb 2.ABSTRACTThe stock of therapeutic weapons available in metastatic colorectal cancer (mCRC) has been progressively grown over the years, with improving both survival and patients' clinical outcome: notwithstanding advances in the knowledge of mCRC biology, as well as advances in treatment, fluoropyrimidine antimetabolite drugs have been for 30 years the mainstay of chemotherapy protocols for this malignancy. 5-Fluorouracil (5FU) seems to act differently depending on administration method: elastomer-mediated continuous infusion better...
Source: Oncotarget - February 22, 2021 Category: Cancer & Oncology Authors: Francesco Jacopo Romano Carmela Barbato Maria Biglietto Vincenzo Di Lauro Dario Arundine Roberto Fiorentino Francesca Ambrosio Maresa Cammarota Bruno Chiurazzi Livio Puglia Sarah Scagliarini Raffaella Ruocco Carmen Mocerino Ivana Cerillo Maria Fiorella Br Source Type: research

Cancer stem cells and macrophages: molecular connections and future perspectives against cancer
Oncotarget. 2021 Feb 2;12(3):230-250. doi: 10.18632/oncotarget.27870. eCollection 2021 Feb 2.ABSTRACTCancer stem cells (CSCs) have been considered the key drivers of cancer initiation and progression due to their unlimited self-renewal capacity and their ability to induce tumor formation. Macrophages, particularly tumor-associated macrophages (TAMs), establish a tumor microenvironment to protect and induce CSCs development and dissemination. Many studies in the past decade have been performed to understand the molecular mediators of CSCs and TAMs, and several studies have elucidated the complex crosstalk that occurs betwee...
Source: Oncotarget - February 22, 2021 Category: Cancer & Oncology Authors: Beatrice Aramini Valentina Masciale Giulia Grisendi Federico Banchelli Roberto D'Amico Antonino Maiorana Uliano Morandi Massimo Dominici Khawaja Husnain Haider Source Type: research

Erratum: GSK3 is required for rapalogs to induce degradation of some oncogenic proteins and to suppress cancer cell growth
Oncotarget. 2021 Feb 2;12(3):251-252. doi: 10.18632/oncotarget.27752. eCollection 2021 Feb 2.ABSTRACT[This corrects the article DOI: 10.18632/oncotarget.3291.].PMID:33613851 | PMC:PMC7869579 | DOI:10.18632/oncotarget.27752 (Source: Oncotarget)
Source: Oncotarget - February 22, 2021 Category: Cancer & Oncology Authors: Junghui Koo Xuerong Wang Taofeek K Owonikoko Suresh S Ramalingam Fadlo R Khuri Shi-Yong Sun Source Type: research

High mRNA expression of LY6 gene family is associated with overall survival outcome in pancreatic ductal adenocarcinoma
Oncotarget. 2021 Feb 2;12(3):145-159. doi: 10.18632/oncotarget.27880. eCollection 2021 Feb 2.ABSTRACTPancreatic cancer ranks one of the worst in overall survival outcome with a 5 year survival rate being less than 10%. Pancreatic cancer faces unique challenges in its diagnosis and treatment, such as the lack of clinically validated biomarkers and the immensely immunosuppressive tumor microenvironment. Recently, the LY6 gene family has received increasing attention for its multi-faceted roles in cancer development, stem cell maintenance, immunomodulation, and association with more aggressive and hard-to-treat cancers. A det...
Source: Oncotarget - February 22, 2021 Category: Cancer & Oncology Authors: Eric Russ Krithika Bhuvaneshwar Guisong Wang Benjamin Jin Michele M Gage Subha Madhavan Yuriy Gusev Geeta Upadhyay Source Type: research

A novel isoform of Homeodomain-interacting protein kinase-2 promotes YAP/TEAD transcriptional activity in NSCLC cells
In this study, we show that a new HIPK2 isoform increases TEAD reporter activity in NSCLC cells. We detected HIPK2 copy number gain in 5/6 (83.3%) NSCLC cell lines. In NSCLC patients with high HIPK2 mRNA expression in the Human Protein Atlas, the five-year survival rate is significantly lower than in patients with low expression (38% vs 47%; p = 0.047). We also found that 70/78 (89.7%) of NSCLC tissues have moderate to strong expression of the N-terminal HIPK2 protein. We detected and cloned a novel HIPK2 isoform 3 and found that its forced overexpression promotes TEAD reporter activity in NSCLC cells. Expressing HIPK2 iso...
Source: Oncotarget - February 22, 2021 Category: Cancer & Oncology Authors: Yuyuan Dai Hiroyuki Kyoyama Yi-Lin Yang Yucheng Wang Shu Liu Yinghao Wang Jian-Hua Mao Zhidong Xu Kazutsugu Uematsu David M Jablons Liang You Source Type: research

Testosterone deficiency in men receiving immunotherapy for malignant melanoma
Oncotarget. 2021 Feb 2;12(3):199-208. doi: 10.18632/oncotarget.27876. eCollection 2021 Feb 2.ABSTRACTImmunotherapy has been established as a standard of care for patients with malignant melanoma, however, the long-term side-effects of immunotherapy are still emerging. Studies over the last decade have documented increasing reports of endocrine dysfunction following the initiation of immunotherapy. Our study aimed to detect the proportion of men who have low testosterone before, during, and or/after receiving immunotherapy for malignant melanoma, and to determine the proportion of men who receive testosterone replacement th...
Source: Oncotarget - February 22, 2021 Category: Cancer & Oncology Authors: Madeline Peters Amy Pearlman William Terry Sarah L Mott Varun Monga Source Type: research

The goal of geroscience is life extension
Oncotarget. 2021 Feb 2;12(3):131-144. doi: 10.18632/oncotarget.27882. eCollection 2021 Feb 2.ABSTRACTAlthough numerous drugs seemingly extend healthspan in mice, only a few extend lifespan in mice and only one does it consistently. Some of them, alone or in combination, can be used in humans, without further clinical trials.PMID:33613842 | PMC:PMC7869575 | DOI:10.18632/oncotarget.27882 (Source: Oncotarget)
Source: Oncotarget - February 22, 2021 Category: Cancer & Oncology Authors: Mikhail V Blagosklonny Source Type: research

Downregulation of SOX2 by inhibition of Usp9X induces apoptosis in melanoma
Oncotarget. 2021 Feb 2;12(3):160-172. doi: 10.18632/oncotarget.27869. eCollection 2021 Feb 2.ABSTRACTMelanoma tumors driven by BRAF mutations often do not respond to BRAF/MEK/ERK pathway inhibitors currently used in treatment. One documented mechanism of resistance is upregulation of SOX2, a transcription factor that is essential for tumor growth and expansion, particularly in melanoma tumors with BRAF mutations. Targeting transcription factors pharmacologically has been elusive for drug developers, limiting treatment options. Here we show that ubiquitin-specific peptidase 9, X-linked (Usp9x), a deubiquitinase (DUB) enzyme...
Source: Oncotarget - February 22, 2021 Category: Cancer & Oncology Authors: Harish Potu Malathi Kandarpa Luke F Peterson Alison Durham Nicholas J Donato Moshe Talpaz Source Type: research

MicroRNA-214 enriched exosomes from human cerebral endothelial cells (hCEC) sensitize hepatocellular carcinoma to anti-cancer drugs
In conclusion, the present in vitro study provides evidence that hCEC-Exo-214 significantly enhances the anti-tumor efficacy of oxaliplatin and sorafenib on HCC cells.PMID:33613846 | PMC:PMC7869574 | DOI:10.18632/oncotarget.27879 (Source: Oncotarget)
Source: Oncotarget - February 22, 2021 Category: Cancer & Oncology Authors: Louie Semaan Qingning Zeng Yong Lu Yi Zhang Mehdi Mohamad Zreik Mohamad Baqer Chamseddine Michael Chopp Zheng Gang Zhang Dilip Moonka Source Type: research

Unravelling actionable biology using transcriptomic data to integrate mitotic index and Ki-67 in the management of lung neuroendocrine tumors
In this study, we investigated the association of mitotic rate and Ki-67 at gene- and pathway-level using transcriptomic data in lung NET malignancies. Lung resection tumor specimens obtained from 28 patients diagnosed with NETs were selected. Mitotic rate, Ki-67 and transcriptomic data were obtained for all samples. The concordance between mitotic rate and Ki-67 was evaluated at gene-level and pathway-level using gene expression data. Our analysis revealed a strong association between mitotic rate and Ki-67 across all samples and cell cycle genes were found to be differentially ranked between them. Pathway analysis indica...
Source: Oncotarget - February 22, 2021 Category: Cancer & Oncology Authors: Venkata S K Manem Olga Sazonova Andr éanne Gagné Mich èle Orain Babak Khoshkrood-Mansoori Nathalie Gaudreault Yohan Boss é Philippe Joubert Source Type: research

Folinic acid in colorectal cancer: esquire or fellow knight? Real-world results from a mono institutional, retrospective study
Oncotarget. 2021 Feb 2;12(3):221-229. doi: 10.18632/oncotarget.27872. eCollection 2021 Feb 2.ABSTRACTThe stock of therapeutic weapons available in metastatic colorectal cancer (mCRC) has been progressively grown over the years, with improving both survival and patients' clinical outcome: notwithstanding advances in the knowledge of mCRC biology, as well as advances in treatment, fluoropyrimidine antimetabolite drugs have been for 30 years the mainstay of chemotherapy protocols for this malignancy. 5-Fluorouracil (5FU) seems to act differently depending on administration method: elastomer-mediated continuous infusion better...
Source: Oncotarget - February 22, 2021 Category: Cancer & Oncology Authors: Francesco Jacopo Romano Carmela Barbato Maria Biglietto Vincenzo Di Lauro Dario Arundine Roberto Fiorentino Francesca Ambrosio Maresa Cammarota Bruno Chiurazzi Livio Puglia Sarah Scagliarini Raffaella Ruocco Carmen Mocerino Ivana Cerillo Maria Fiorella Br Source Type: research

Cancer stem cells and macrophages: molecular connections and future perspectives against cancer
Oncotarget. 2021 Feb 2;12(3):230-250. doi: 10.18632/oncotarget.27870. eCollection 2021 Feb 2.ABSTRACTCancer stem cells (CSCs) have been considered the key drivers of cancer initiation and progression due to their unlimited self-renewal capacity and their ability to induce tumor formation. Macrophages, particularly tumor-associated macrophages (TAMs), establish a tumor microenvironment to protect and induce CSCs development and dissemination. Many studies in the past decade have been performed to understand the molecular mediators of CSCs and TAMs, and several studies have elucidated the complex crosstalk that occurs betwee...
Source: Oncotarget - February 22, 2021 Category: Cancer & Oncology Authors: Beatrice Aramini Valentina Masciale Giulia Grisendi Federico Banchelli Roberto D'Amico Antonino Maiorana Uliano Morandi Massimo Dominici Khawaja Husnain Haider Source Type: research

Erratum: GSK3 is required for rapalogs to induce degradation of some oncogenic proteins and to suppress cancer cell growth
Oncotarget. 2021 Feb 2;12(3):251-252. doi: 10.18632/oncotarget.27752. eCollection 2021 Feb 2.ABSTRACT[This corrects the article DOI: 10.18632/oncotarget.3291.].PMID:33613851 | PMC:PMC7869579 | DOI:10.18632/oncotarget.27752 (Source: Oncotarget)
Source: Oncotarget - February 22, 2021 Category: Cancer & Oncology Authors: Junghui Koo Xuerong Wang Taofeek K Owonikoko Suresh S Ramalingam Fadlo R Khuri Shi-Yong Sun Source Type: research

High mRNA expression of LY6 gene family is associated with overall survival outcome in pancreatic ductal adenocarcinoma
Oncotarget. 2021 Feb 2;12(3):145-159. doi: 10.18632/oncotarget.27880. eCollection 2021 Feb 2.ABSTRACTPancreatic cancer ranks one of the worst in overall survival outcome with a 5 year survival rate being less than 10%. Pancreatic cancer faces unique challenges in its diagnosis and treatment, such as the lack of clinically validated biomarkers and the immensely immunosuppressive tumor microenvironment. Recently, the LY6 gene family has received increasing attention for its multi-faceted roles in cancer development, stem cell maintenance, immunomodulation, and association with more aggressive and hard-to-treat cancers. A det...
Source: Oncotarget - February 22, 2021 Category: Cancer & Oncology Authors: Eric Russ Krithika Bhuvaneshwar Guisong Wang Benjamin Jin Michele M Gage Subha Madhavan Yuriy Gusev Geeta Upadhyay Source Type: research

A novel isoform of Homeodomain-interacting protein kinase-2 promotes YAP/TEAD transcriptional activity in NSCLC cells
In this study, we show that a new HIPK2 isoform increases TEAD reporter activity in NSCLC cells. We detected HIPK2 copy number gain in 5/6 (83.3%) NSCLC cell lines. In NSCLC patients with high HIPK2 mRNA expression in the Human Protein Atlas, the five-year survival rate is significantly lower than in patients with low expression (38% vs 47%; p = 0.047). We also found that 70/78 (89.7%) of NSCLC tissues have moderate to strong expression of the N-terminal HIPK2 protein. We detected and cloned a novel HIPK2 isoform 3 and found that its forced overexpression promotes TEAD reporter activity in NSCLC cells. Expressing HIPK2 iso...
Source: Oncotarget - February 22, 2021 Category: Cancer & Oncology Authors: Yuyuan Dai Hiroyuki Kyoyama Yi-Lin Yang Yucheng Wang Shu Liu Yinghao Wang Jian-Hua Mao Zhidong Xu Kazutsugu Uematsu David M Jablons Liang You Source Type: research

Testosterone deficiency in men receiving immunotherapy for malignant melanoma
Oncotarget. 2021 Feb 2;12(3):199-208. doi: 10.18632/oncotarget.27876. eCollection 2021 Feb 2.ABSTRACTImmunotherapy has been established as a standard of care for patients with malignant melanoma, however, the long-term side-effects of immunotherapy are still emerging. Studies over the last decade have documented increasing reports of endocrine dysfunction following the initiation of immunotherapy. Our study aimed to detect the proportion of men who have low testosterone before, during, and or/after receiving immunotherapy for malignant melanoma, and to determine the proportion of men who receive testosterone replacement th...
Source: Oncotarget - February 22, 2021 Category: Cancer & Oncology Authors: Madeline Peters Amy Pearlman William Terry Sarah L Mott Varun Monga Source Type: research