AKT1 and SELP Polymorphisms Predict the Risk of Developing Cachexia in Pancreatic Cancer Patients

Avan, Abolfazl; Avan, Amir; Large, Tessa Y.S. Le; Mambrini, Andrea; Funel, Niccola; Maftouh, Mina; Ghayour‐Mobarhan, Majid; Cantore, Maurizio; Boggi, Ugo; Peters, Godefridus J.; Pacetti, Paola; Giovannetti, Elisa

doi:10.1371/journal.pone.0108057

Cited by 41 publications

(44 citation statements)

References 45 publications

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“…In the present study, SELP and AKT1 SNPs were analyzed and significant association was found on AKT1, where the risk of 5% weight loss in patients with the AKT1 A allele significantly increased. This finding was in the same trend as that reported by Avan et al [4], suggesting that the AKT1 A allele may play a key role in the development of cancer cachexia. There were no significant effects of the SNPs examined on patients' survival, presumably due to the relatively smaller sample size of the present study.…”

Section: Discussionsupporting

confidence: 91%

“…One previous study suggested that SELP and AKT1 polymorphisms may play roles in the risk of cachexia and death in pancreatic ductal adenocarcinoma patients (PDAC) in Caucasians [4]. In the present study, SELP and AKT1 SNPs were analyzed and significant association was found on AKT1, where the risk of 5% weight loss in patients with the AKT1 A allele significantly increased.…”

Section: Discussionmentioning

confidence: 58%

“…AKT1 is shown to exert its effects through various mediators, such as protein kinases and phosphatases, survival factors, regulators of protein synthesis, and so on, thereby play key roles in the development of cancer, cardiovascular diseases or metabolic diseases [12]. In human cancer cachexia, reduced activity of AKT1 in those with AKT1 rs1130233 G/A+A/A genotypes is considered to favor the induction of apoptosis, resulting in the higher risk of muscle atrophy and cachexia [4]. In the body of cachexia patients, production of inflammatory cytokine is induced, leading to the breakdown of fat and muscle.…”

Section: Discussionmentioning

confidence: 99%

“…There are large amount of patients' clinical data such as weight, muscle weight of the patients collected and accumulated in the hospital. AKT1 (AKT serine/threonine kinase 1) and SELP (selectin P) polymorphisms are involved in cancer cachexia in pancreatic patients in Caucasians [4]. Polymorphisms of ICAM1 (intercellular adhesion molecule 1) can be a potentially useful biomarker for identifying individuals with higher risk of gastric cancer, predicting disease progression, and guiding individualized treatment [5].…”

Section: Introductionmentioning

confidence: 99%

“…polymorphisms of AKT1 rs1130233, ICAM1 rs281432, SELP rs6128 and TNSRSF1A rs4149570, which have been recently suggested to be associated with the risk of cachexia/weight loss in Caucasian cancer patients [4], together with the LIF rs929271, and the risk of cancer cachexia as well as patients' prognosis in Japanese, leveraging the data from the cancer outpatient clinic of our hospital to find the way for the possible personalized palliative care of gastrointestinal patients based on genetic information.…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Clinical Impact of the AKT1 rs1130233 SNP in Japanese Gastrointestinal Cancer Patients with Palliative Care

Morishita¹,

Hishida²,

Okugawa³

et al. 2017

J Palliat Care Med

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 58%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Clinical Impact of the AKT1 rs1130233 SNP in Japanese Gastrointestinal Cancer Patients with Palliative Care

Morishita¹,

Hishida²,

Okugawa³

et al. 2017

J Palliat Care Med

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AMP‐kinase inhibitor dorsomorphin reduces the proliferation and migration behavior of colorectal cancer cells by targeting the AKT/mTOR pathway

et al. 2019

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Colorectal cancer (CRC) is among the leading causes of cancer-related mortality, despite extensive efforts in the identification of new treatment options. Hence, there is a need for the development of novel agents with therapeutic potential in treatment of CRC. Dorsomorphin has demonstrated antiproliferative activity against different malignancies. Here we have investigated the pharmaceutical potential of dorsomorphin in two-dimensional and three-dimensional cell-culture models of CRC. The antiproliferative, antimigratory, apoptotic activity and effect of this agent on cell cycle was evaluated by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, wound healing assay, and flow cytometry, respectively, while the expression of genes involved in Wnt/Pi3K pathways was assessed at mRNA and/or proteins by reverse transcription polymerase chain reaction (RT-PCR) or western blot. Dorsomorphin inhibited CRC cell growth by modulating the cyclinD1, surviving and p-Akt. This agent was able to reduce the migratory behaviors of CRC cells, compared to control cells, through perturbation of E-cadherin. Also our data showed that dorsomorphin enhanced the percentage of the cells in sub-G1 and induced apoptosis in both late/early stages, as detected by annexin V. Also the regulatory effect of dorsomorphin on oxidant/antioxidant balance was assessed by cellular reactive oxygen species (ROS) generation. In particular, these data showed that dorsomorphin markedly increased the ROS production in CRC cells. Our finding demonstrated that dorsomorphin antagonizes cell growth and migration, through perturbation of Akt/mTOR/Wnt pathways in CRC, supporting further studies on the therapeutic potential of this novel anticancer agent in treatment of CRC. K E Y W O R D S colorectal cancer, dorsomorphin, Wnt/PI3K/Akt -pathwayAbbreviations: AMPK, AMP-activated protein kinase; BMP, bone morphogenetic protein; CRC, colorectal cancer; DMEM, Dulbecco Modified Eagle Medium; EGFR, epidermal growth factor receptor; FHKR, forkhead transcription factor; GSK3β, glycogen synthase kinase 3β; PI, propidium iodide; PI3k/Akt, phosphatidylinositol 3-kinase/protein kinase B; ROS, reactive oxygen species.† Sadaf Ghanaatgar-Kasbi and Forouzan Amerizadeh contributed equally to the study and are the first co-authors.

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Crocin synergistically enhances the antiproliferative activity of 5‐flurouracil through Wnt/PI3K pathway in a mouse model of colitis‐associated colorectal cancer

Amerizadeh

Rezaei

Rahmani

et al. 2018

J of Cellular Biochemistry

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Colorectal cancer (CRC) is the third most common cause of cancer-related death, and hence there is a need for the identification of novel-agents to improve the efficacy of existing therapies. There is growing evidence for the antitumor activity of crocin, although its activity and molecular mechanisms in CRC remains to be elucidated. Here we explored the therapeutic application of crocin or its combination with 5-flurouracil in a mouse model of colitis-associated colon cancer. The antiproliferative activity of crocin was assessed in two-dimensional and three-dimensional cell-culture models. The migratory behaviors were determined, while the expression levels of several genes were assessed by quantitative reverse transcriptase polymerase chain reaction/Western blot analysis. We examined the anti-inflammatory properties of crocin by pathological evaluation and disease-activity index as well as oxidative or antioxidant markers: malondialdehyde (MDA) and total-thiols (T-SH) levels and superoxide dismutase (SOD) and catalase (CAT) activity. Crocin suppressed cell-growth and the invasive behavior of CRC cells through modulation of the Wnt-pathway and E-cadherin. Moreover, administration of crocin alone, or in combination with 5-FU dramatically reduced the tumor number and tumor size in both distal/mid-colon followed by reduction in disease-activity index. Crocin also suppressed the colonic inflammation induced by dextran-sulfate-sodium and notably recovered the increased levels of MDA, decreased thiol levels and activity of CAT levels. Crocin was able to ameliorate the severe inflammation with mucosal ulcers and high-grade dysplastic crypts as detected by inflammation score, crypt loss, pathological changes and histology scores. We demonstrated an antitumor activity of crocin in CRC and its potential role in improvement of inflammation with mucosal ulcers and high-grade dysplastic crypts, supporting the desireability of further investigations on the therapeutic potential of this approach in CRC.

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AKT1 and SELP Polymorphisms Predict the Risk of Developing Cachexia in Pancreatic Cancer Patients

Cited by 41 publications

References 45 publications

Clinical Impact of the AKT1 rs1130233 SNP in Japanese Gastrointestinal Cancer Patients with Palliative Care

Clinical Impact of the AKT1 rs1130233 SNP in Japanese Gastrointestinal Cancer Patients with Palliative Care

AMP‐kinase inhibitor dorsomorphin reduces the proliferation and migration behavior of colorectal cancer cells by targeting the AKT/mTOR pathway

Crocin synergistically enhances the antiproliferative activity of 5‐flurouracil through Wnt/PI3K pathway in a mouse model of colitis‐associated colorectal cancer

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