scholarly journals Serotonin Pathway in Cancer

2021 ◽  
Vol 22 (3) ◽  
pp. 1268
Author(s):  
Pragathi Balakrishna ◽  
Sagila George ◽  
Hassan Hatoum ◽  
Sarbajit Mukherjee
Keyword(s):  
Therapeutic Target ◽  
Tryptophan Hydroxylase ◽  
Underlying Mechanism ◽  
Serotonin Release ◽  
In Vivo Studies ◽  
Receptor Subtypes ◽  
Cancer Pathogenesis ◽  
Serotonin Pathway

Serotonin (5-hydroxytryptamine, 5-HT) is a biogenic monoamine produced from the essential amino acid tryptophan. Serotonin’s role as a neurotransmitter in the central nervous system and a motility mediator in the gastrointestinal tract has been well defined, and its function in tumorigenesis in various cancers (gliomas, carcinoids, and carcinomas) is being studied. Many studies have shown a potential stimulatory effect of serotonin on cancer cell proliferation, invasion, dissemination, and tumor angiogenesis. Although the underlying mechanism is complex, it is proposed that serotonin levels in the tumor and its interaction with specific receptor subtypes are associated with disease progression. This review article describes serotonin’s role in cancer pathogenesis and the utility of the serotonin pathway as a potential therapeutic target in cancer treatment. Octreotide, an inhibitor of serotonin release, is used in well-differentiated neuroendocrine cancers, and the tryptophan hydroxylase (TPH) inhibitor, telotristat, is currently being investigated in clinical trials to treat patients with metastatic neuroendocrine tumors and advanced cholangiocarcinoma. Several in vitro studies have shown the anticancer effect of 5-HT receptor antagonists in various cancers such as prostate cancer, breast cancer, urinary bladder, colorectal cancer, carcinoid, and small-cell lung cancer. More in vivo studies are needed to assess serotonin’s role in cancer and its potential use as an anticancer therapeutic target. Serotonin is also being evaluated for its immunoregulatory properties, and studies have shown its potential anti-inflammatory effect. Therefore, it would be of interest to explore the combination of serotonin antagonists with immunotherapy in the future.

scholarly journals Epigenetic roles of PIWI proteins and piRNAs in lung cancer

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Hadis Fathizadeh ◽  
Zatollah Asemi
Keyword(s):  
Lung Cancer ◽  
Molecular Mechanisms ◽  
Treatment Strategies ◽  
High Mobility ◽  
P Element ◽  
In Vivo Studies ◽  
Cancer Pathogenesis ◽  
Non Coding Rnas

AbstractLung cancer is one of very important malignancies which are related to high mobility and mortality in the world. Despite several efforts for improving diagnosis and treatment strategies of lung cancer, finding and developing new and effective therapeutic and diagnostic are needed. A variety of internal and external factors could be involved in lung cancer pathogenesis. Among internal factors, epigenetic mechanisms have been emerged as very important players in the lung cancer. Non-coding RNAs is known as one of epigenetic regulators which exert their effects on a sequence of cellular and molecular mechanisms. P-element induced wimpy testis (PIWI)-interacting RNAs (piRNAs or piR) is one of small non-coding RNAs that the deregulation of these molecules is associated with initiation and progression of different cancers such as lung cancer. Several activities are related to PIWI/piRNA pathway such as suppression of transposons and mobile genetic elements. In vitro and in vivo studies demonstrated the upregulation or downregulation of PIWI proteins and piRNAs could lead to the increasing of cell proliferation, apoptosis reduction and promoting tumor growth in the lung cancer. Hence, PIWI proteins and piRNA could be introduced as new diagnostic and therapeutic biomarkers in the lung cancer therapy. Herein, we have focused on PIWI proteins and piRNA functions and their impact on the progression of lung cancer.

REG4 as a novel biomarker of lung adenocarcinoma with mutated KRAS and TTF-1 low expression.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e14541-e14541
Author(s):  
Hui Yu ◽  
Si Sun
Keyword(s):  
Lung Adenocarcinoma ◽  
Rna Sequencing ◽  
Underlying Mechanism ◽  
Clinical Samples ◽  
Cancer Center ◽  
Pcr Analysis ◽  
Cancer Pathogenesis ◽  
Low Expression

e14541 Background: Recent research has classified lung adenocarcinoma patients with KRAS mutation into three subtypes by co-occurring genetic events in TP53 (KP subgroup), STK11/LKB1 (KL subgroup) and CDKN2A/B inactivation coupled with low expression of the TTF-1 (KC subgroup). The aim of this study was to identify novel biomarkers through searching the candidate molecules that contributing to lung adenocarcinoma pathogenesis, especially KC subtype. Methods: We analyzed the publicly available database and identified the candidate REG4 using the E-GEOD-31210 dataset, and then confirmed by TCGA dataset. In addition, an independent cohort of 55 clinical samples was analyzed by quantitative real-time PCR analysis. Functional studies and RNA sequencing were performed after the silencing REG4 expression. Results: REG4, an important regulator of gastro-intestinal carcinogenesis, was highly expressed in KRAS mutated lung adenocarcinoma with low expression of TTF-1 (KC subtype). The results were validated both by gene expression analysis and immunohistochemistry study in an independent 55 clinical samples from Fudan University Shanghai Cancer Center. Further in vitro and in vivo functional assays revealed silencing REG4 expression significantly reduce cancer cell proliferation and tumorigenesis. Moreover, RNA sequencing and GSEA analysis displayed that REG4 knockdown might induce the cell cycle arrest by regulating G2/M checkpoint and E2F targets. Conclusions: Our results indicate that REG4 plays an important role in KRAS-driven lung cancer pathogenesis and is a novel biomarker of lung adenocarcinoma subtype. Future studies are required to clarify the underlying mechanism of REG4 in the division and proliferation of KC tumors and its potential therapeutic value.

scholarly journals Photothermal ablation of murine melanomas by Fe3O4 nanoparticle clusters

2021 ◽  
Author(s):  
Xue Wang ◽  
Lili Xuan ◽  
Ying Pan
Keyword(s):  
Near Infrared ◽  
Underlying Mechanism ◽  
Local Heat ◽  
In Vivo Studies ◽  
Infrared Light ◽  
Microscopy Imaging ◽  
Development Of Resistance ◽  
Nanoparticle Clusters

Melanoma is one of the deadliest forms of cancer, for which therapeutic regimens are usually limited by the development of resistance. Here, we fabricated the Fe3O4 nanoparticle clusters (NPCs) that have drawn widespread attention and investigated their role in the treatment of melanoma by photothermal therapy (PTT). Transmission electron microscopy imaging shows that our synthesized NPCs are spherically shaped with an averaged diameter of 329.2 nm. They are highly absorptive at the near-infrared 808 nm wavelength and efficient at converting light into local heat. In vitro experiments using light-field microscopy and MTT assay showed that Fe3O4 NPCs, in conjunction with near-infrared irradiation, effectively ablated A375 melanoma cells by inducing overt apoptosis. Consistently, in vivo studies using BALB/c mice found that intratumoral administration of Fe3O4 NPCs and concomitant in situ exposure to near-infrared light significantly inhibited growth of implanted tumor xenografts. Finally, we revealed, by experimental approaches including semi-quantitative PCR, western blot and immunohistochemistry, the heat shock protein HSP70 to be upregulated in response to PTT, suggesting this chaperone protein could be a plausible underlying mechanism for the observed therapeutic outcome. Altogether, our results highlight the promise of Fe3O4 NPCs as a new PTT option to treat melanoma.

scholarly journals Metallopanstimulin-1 (MPS-1) mediates the promotion effect of leptin on colorectal cancer through activation of JNK/c-Jun signaling pathway

2019 ◽  
Vol 10 (9) ◽  
Author(s):  
Dongxing Cao ◽  
Yang Luo ◽  
Shaolan Qin ◽  
Minhao Yu ◽  
Yifei Mu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Underlying Mechanism ◽  
In Vivo Studies ◽  
Advanced Tumor Stage ◽  
Poor Overall Survival ◽  
Promotion Effect ◽  
Over Expression ◽  
Advanced Tumor

Abstract Obesity is a major epigenetic cause for colorectal cancer (CRC). Leptin is implicated in obesity-associated CRC, but the underlying mechanism remains unclear. The current study identified over-expression of metallopanstimulin-1 (MPS-1) in CRC patients through microarray and histological analysis, especially in obese CRC patients. MPS-1 was correlated with advanced tumor stage, suggesting its association with CRC progression. In addition, MPS-1 over-expression was associated with poor overall survival (OS) in obese CRC patients, but not in their non-obese counterparts, suggesting its potential as a prognostic marker of obese CRC patients. MPS-1 expression was positively associated with circulating leptin levels in CRC patients, especially in obese cases. Functional experiments demonstrated that MPS-1 silencing inhibited tumor proliferation and colony formation, and induced apoptosis of CRC cells in vitro. Converse results were obtained from the experiments with MPS-1 over-expression. Mechanistically, MPS-1 executed its action through induction of c-Jun N-terminal kinase (JNK)/c-Jun pathway. Moreover, the promotion effect of MPS-1 on CRC progression was modulated by leptin. In vivo studies demonstrated that MPS-1 silencing suppressed tumor growth of CRC via inhibiting JNK/c-Jun signaling. Collectively, this study indicates that MPS-1 promotes leptin-induced CRC via activating JNK/c-Jun pathway. MPS-1 might represent a potent candidate for the treatment and prognostic prediction of obesity-associated CRC.

Eplerenone Prevents Atrial Fibrosis via the TGF-β Signaling Pathway

Cardiology ◽  
2017 ◽  
Vol 138 (1) ◽  
pp. 55-62 ◽  
Author(s):  
Lili Du ◽  
Mu Qin ◽  
Yi Yi ◽  
Xiaoqing Chen ◽  
Weifeng Jiang ◽  
...  
Keyword(s):  
Protein Expression ◽  
Western Blotting ◽  
Feedback Regulation ◽  
Underlying Mechanism ◽  
In Vivo Studies ◽  
Atrial Fibrosis ◽  
Qrt Pcr ◽  
Tgf Β1

Objectives: Eplerenone (EPL), an antagonist of the mineralocorticoid receptor, is beneficial for atrial fibrillation and atrial fibrosis. However, the underlying mechanism remains less well known. We aimed to investigate the effect of EPL on atrial fibrosis using a mouse with selective atrial fibrosis and to explore the underlying mechanisms. Methods: EPL-treated MHC-TGFcys33ser transgenic mice that have selective atrial fibrosis (Tx+EPL mice), as well as control mice, were used for in vivo studies including histological analyses, Western blotting, and qRT-PCR studies. TGF-β1-stimulated atrial fibroblasts were treated with EPL or vehicle for the in vitro studies including Western blotting and qRT-PCR studies. In addition, Smad7 siRNA was used to knock down Smad7. Results: EPL inhibited atrial fibrosis in the Tx mice. In addition, EPL suppressed the expression of fibrosis-related molecules induced by TGF-β1 in vivo and in vitro. This occurred in concert with a downregulation of Smad7 protein expression and an upregulation of p-Smad2/3 protein expression. In addition, knockdown of Smad7 by siRNA abolished the protective roles of EPL. Conclusions: EPL inhibited atrial fibrosis in Tx mice. The underlying mechanism may involve increased protein expression of Smad7, which enhances the inhibitory feedback regulation of TGF-β1/Smad signaling.

scholarly journals Evaluating the Effect of Lenvatinib on Sorafenib-Resistant Hepatocellular Carcinoma Cells

2021 ◽  
Vol 22 (23) ◽  
pp. 13071
Author(s):  
Tingting Shi ◽  
Hisakazu Iwama ◽  
Koji Fujita ◽  
Hideki Kobara ◽  
Noriko Nishiyama ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Systemic Treatment ◽  
Underlying Mechanism ◽  
Erk Signaling ◽  
In Vivo Studies ◽  
Cross Resistance ◽  
First Line ◽  
Patient Response

Hepatocellular carcinoma (HCC) is one of the major causes of cancer-related deaths worldwide. Sorafenib has been used as a first-line systemic treatment for over a decade. However, resistance to sorafenib limits patient response and presents a major hurdle during HCC treatment. Lenvatinib has been approved as a first-line systemic treatment for advanced HCC and is the first agent to achieve non-inferiority against sorafenib. Therefore, in the present study, we evaluated the inhibition efficacy of lenvatinib in sorafenib-resistant HCC cells. Only a few studies have been conducted on this topic. Two human HCC cell lines, Huh-7 and Hep-3B, were used to establish sorafenib resistance, and in vitro and in vivo studies were employed. Lenvatinib suppressed sorafenib-resistant HCC cell proliferation mainly by inducing G1 cell cycle arrest through ERK signaling. Hep-3B sorafenib-resistant cells showed partial cross-resistance to lenvatinib, possibly due to the contribution of poor autophagic responsiveness. Overall, the findings suggest that the underlying mechanism of lenvatinib in overcoming sorafenib resistance in HCC involves FGFR4-ERK signaling. Lenvatinib may be a suitable second-line therapy for unresectable HCC patients who have developed sorafenib resistance and express FGFR4.

scholarly journals BRD4 as a therapeutic target for nonfunctioning and growth hormone pituitary adenoma

2020 ◽  
Vol 22 (8) ◽  
pp. 1114-1125
Author(s):  
Chengzhang Shi ◽  
Zhao Ye ◽  
Jie Han ◽  
Xiaoqing Ye ◽  
Wenchao Lu ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Pituitary Adenoma ◽  
Therapeutic Target ◽  
Expression Patterns ◽  
B Cell Lymphoma ◽  
In Vivo Studies ◽  
Radical Excision ◽  
Western Blots

Abstract Background Nonfunctioning pituitary adenoma (NFPA) and growth hormone pituitary adenoma (GHPA) are major subtypes of pituitary adenomas (PAs). The primary treatment is surgical resection. However, radical excision remains challenging, and few effective medical therapies are available. It is urgent to find novel targets for the treatment. Bromodomain-containing protein 4 (BRD4) is an epigenetic regulator that leads to aberrant transcriptional activation of oncogenes. Herein, we investigated the pathological role of BRD4 and evaluated the effectiveness of BRD4 inhibitors in the treatment of NFPA and GHPA. Methods The expression of BRD4 was detected in NFPA, GHPA, and normal pituitary tissues. The efficacies of BRD4 inhibitors were evaluated in GH3 and MMQ cell lines, patient-derived tumor cells, and in vivo mouse xenograft models of PA. Standard western blots, real-time PCR, and flow cytometry experiments were performed to investigate the effect of BRD4 inhibitors on cell cycle progression, apoptosis, and the expression patterns of downstream genes. Results Immunohistochemistry studies demonstrated the overexpression of BRD4 in NFPA and GHPA. In vitro and in vivo studies showed that treatment with the BRD4 inhibitor ZBC-260 significantly inhibited the proliferation of PA cells. Further mechanistic studies revealed that ZBC-260 could downregulate the expression of c-Myc, B-cell lymphoma 2 (Bcl2), and related genes, which are vital factors in pituitary tumorigenesis. Conclusion In this study, we determined the overexpression of BRD4 in NFPA and GHPA and assessed the effects of BRD4 inhibitors on PA cells in vitro and in vivo. Our findings suggest that BRD4 is a promising therapeutic target for NFPA and GHPA.

The Impact of Polyphenolic in The Management of Breast Cancer: Mechanistic Aspects and Recent Patents

2021 ◽  
Vol 16 ◽  
Author(s):  
Heba A.S. El-Nashar ◽  
Shaza H. Aly ◽  
Amirhossein Ahmadi ◽  
Mohamed El-Shazly
Keyword(s):  
Breast Cancer ◽  
Therapeutic Potential ◽  
Treatment Strategies ◽  
Underlying Mechanism ◽  
In Vivo Studies ◽  
Molecular Characteristics ◽  
Anticancer Properties ◽  
The Impact

Background: Breast cancer is the most frequently diagnosed type of cancer in women (2.1 million) and stands as the fifth leading cause of death. Several treatment strategies are available such as surgical resection, radiation, hormonal therapy, and conventional chemotherapy that are associated with severe adverse effects on the patients. Objective: This review aims to summarize the different studies (in vitro, in vivo, and new patents) concerning the therapeutic potential of plant polyphenolics in the management of breast cancer published in the period from January 2016 to January 2021. Moreover, this review will focus on the underlying mechanism of action and molecular characteristics of these compounds. Methods: The data of this review were collected from different scientific databases such as PubMed, Science Direct, Google Scholarship, sci-finder, and Egyptian Knowledge bank (EKB). Results: During the last period (2016-2021), the in vitro studies investigated about 52 natural compounds of polyphenolic nature with promising anti-breast cancer, while fourteen compounds were reported via in vivo studies. Besides, there were about fifteen compounds registered as patent drugs. Different mechanisms of action and molecular targets were reported to provide a great clarified base and precise reflection for the anticancer properties of these compounds against breast cancer. Conclusion: Polyphenolics represent a plentiful sources of anticancer lead compounds that stand against the progression of breast cancer invasion and metastasis.

scholarly journals No loss of sst receptors gene expression in advanced stages of colorectal cancer

1999 ◽  
pp. 362-366 ◽  
Author(s):  
V Vuaroqueaux ◽  
A Dutour ◽  
N Briard ◽  
G Monges ◽  
M Grino ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Mrna Expression ◽  
Somatostatin Analogs ◽  
In Vivo Studies ◽  
Receptor Subtypes ◽  
Large Set ◽  
Inhibitory Peptide ◽  
Advanced Stages

As demonstrated by several studies, the pan-inhibitory peptide somatostatin (SS) is implicated in a large variety of physiological processes in the gastrointestinal tractus. SS inhibits hormonal and gastric acid secretions, and decreases gastric and intestinal motility, mesenteric blood flow and intestinal absorption. In vitro and in vivo studies showed also that the antiproliferative potency of SS analogs may be a target to improve the prognosis of colorectal cancer. Here we report the expression profile of the five SS receptor subtypes (hsst1-5) mRNAs in a large set of tumoral and normal colon. Using reverse transcription-PCR, we showed that hsst5, hsst1 and hsst2 mRNA subtypes were the most frequently expressed hsst mRNA subtypes in normal and pathological colon. Interestingly, we found that the frequency of hsst5 mRNA expression in the left colon was significantly higher in tumors than in normal samples: 81. 2% (13/16) and 36.4% (4/11) respectively (0.025>P>0.01, chi2 test with Yates' correction). We did not find any influence of Dukes' stage on hsst mRNAs expression. Of interest, no loss of hsst2 and hsst5 mRNA expression in advanced stages was noted. Some differences in the frequency of expression of hsst mRNAs according to the origin of the tissue (left or right colon) were evident. The expression of hsst5 and hsst2 mRNA in advanced colorectal carcinoma associated with the development of new SS analogs boost the relevance of colorectal cancer treatment by somatostatin analogs.

Can diallyl trisulfide, a dietary garlic-derived compound, activate ferroptosis to overcome therapy resistance in prostate cancer?

2021 ◽  
pp. 026010602110183
Author(s):  
Angela Lincy Prem Antony Samy ◽  
Dhruvi Shah ◽  
Preksha Shahagadkar ◽  
Hillary Shah ◽  
Gnanasekar Munirathinam
Keyword(s):  
Prostate Cancer ◽  
Cell Death ◽  
Organosulfur Compound ◽  
Underlying Mechanism ◽  
Therapy Resistance ◽  
In Vivo Studies ◽  
Diallyl Trisulfide ◽  
Apoptosis Resistance

Background: Therapy resistance is the underlying reason for poor outcome in prostate cancer (PCa) patients. Diallyl trisulfide (DATS) is an organosulfur compound present in garlic. DATS has been shown to target PCa cells by induction of apoptosis, increase in the production of reactive oxygen species, degradation of ferritin protein and increase in the labile iron (Fe) pool. Aim: We hypothesize that DATS could induce ferroptosis, an Fe-dependent, unique non-apoptotic form of regulated cell death to eliminate therapy resistance encountered by PCa patients. Methods: In vitro and in vivo studies should be performed to test the hypothesis. Results: As per the hypothesis, DATS would eliminate apoptotic resistance via inducing ferroptosis. Conclusion: Since apoptosis resistance has been reported to be the underlying mechanism of therapy resistance in PCa, DATS could be used to effectively target PCa cells by overcoming apoptosis resistance and inducing ferroptosis-mediated cell death of PCa cells.

Sign in / Sign up

Export Citation Format

Share Document