A systems medicine approach for finding target proteins affecting treatment outcomes in patients with non-Hodgkin lymphoma

Ajorloo, Faezeh; Vaezi, Mohammad; Saadat, Alireza; Safaee, Seyed Reza; Gharib, Behrouz; Ghanei, Mostafa; Siadat, Seyed Davar; Vaziri, Farzam; Fateh, Abolfazl; Pazhouhandeh, Mehrdad; Vaziri, Behrouz; Moazemi, Reza; Mahboudi, Fereidoun; Jamnani, Fatemeh Rahimi

doi:10.1371/journal.pone.0183969

Cited by 11 publications

(20 citation statements)

References 148 publications

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“…history of diseases in patients and their families) [20,21]. The blood level of C-reactive protein ( 6 mg/dl), erythrocyte sedimentation rate ( 32 mm/h), rheumatoid factor (negative RF), complete blood cell count and chest X-ray were examined in the patients.…”

Section: Subjectsmentioning

confidence: 99%

“…The sera of healthy controls, NDP and RP groups were mixed separately and IgG was purified with the Melon TM Gel IgG Purification Kit (Pierce, Rockford, IL, USA), according to the manufacturer's instruction [21].…”

Section: Igg Purification From the Seramentioning

confidence: 99%

“…According to the manufacturer's instruction, the Ph.D. TM -C7C phage display peptide library kit (New England Biolabs, Beverly, MA, USA) was used to perform three successive cycles of biopanning on purified IgG of the NDP and RP groups [21].…”

Section: Biopanning On Purified Iggmentioning

confidence: 99%

“…The specificity of 50 phage clones from biopanning on the NDP and RP IgG was evaluated separately by monoclonal phage ELISA, based on the Ph.D. TM -C7C kit instruction (Supporting information) [21,22]. The specificity of 50 phage clones from biopanning on the NDP and RP IgG was evaluated separately by monoclonal phage ELISA, based on the Ph.D. TM -C7C kit instruction (Supporting information) [21,22].…”

Section: Biopanning On Purified Iggmentioning

confidence: 99%

“…By running the modularity function, the nodes were coloured differently and laid out circularly based on their modules. Literature data-mining was also performed to find out the contribution of pathways and hubs to MS, DMT and cancer [21]. pharm.mssm.edu/Enrichr/) [27] web tools, respectively.…”

Section: Network Visualization Gene Ontology (Go) and Pathway Enrichmentioning

confidence: 99%

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A systems medicine approach reveals disordered immune system and lipid metabolism in multiple sclerosis patients

Pazhouhandeh

Sahraian

Siadat

et al. 2018

Clinical and Experimental Immunology

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Identification of autoimmune processes and introduction of new autoantigens involved in the pathogenesis of multiple sclerosis (MS) can be helpful in the design of new drugs to prevent unresponsiveness and side effects in patients. To find significant changes, we evaluated the autoantibody repertoires in newly diagnosed relapsing-remitting MS patients (NDP) and those receiving disease-modifying therapy (RP). Through a random peptide phage library, a panel of NDP- and RP-specific peptides was identified, producing two protein data sets visualized using Gephi, based on protein--protein interactions in the STRING database. The top modules of NDP and RP networks were assessed using Enrichr. Based on the findings, a set of proteins, including ATP binding cassette subfamily C member 1 (ABCC1), neurogenic locus notch homologue protein 1 (NOTCH1), hepatocyte growth factor receptor (MET), RAF proto-oncogene serine/threonine-protein kinase (RAF1) and proto-oncogene vav (VAV1) was found in NDP and was involved in over-represented terms correlated with cell-mediated immunity and cancer. In contrast, transcription factor RelB (RELB), histone acetyltransferase p300 (EP300), acetyl-CoA carboxylase 2 (ACACB), adiponectin (ADIPOQ) and phosphoenolpyruvate carboxykinase 2 mitochondrial (PCK2) had major contributions to viral infections and lipid metabolism as significant events in RP. According to these findings, further research is required to demonstrate the pathogenic roles of such proteins and autoantibodies targeting them in MS and to develop therapeutic agents which can ameliorate disease severity.

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Section: Subjectsmentioning

confidence: 99%

Section: Igg Purification From the Seramentioning

confidence: 99%

Section: Biopanning On Purified Iggmentioning

confidence: 99%

Section: Biopanning On Purified Iggmentioning

confidence: 99%

Section: Network Visualization Gene Ontology (Go) and Pathway Enrichmentioning

confidence: 99%

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A systems medicine approach reveals disordered immune system and lipid metabolism in multiple sclerosis patients

Pazhouhandeh

Sahraian

Siadat

et al. 2018

Clinical and Experimental Immunology

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Rutin restrains the growth and metastasis of mouse breast cancer cells by regulating the microRNA‐129‐1‐3p‐mediated calcium signaling pathway

et al. 2021

J Biochem & Molecular Tox

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Breast cancer is a common malignancy that is highly lethal. Due to the poor prognosis, more effective and efficient treatment methods are urgently needed. Rutin (RUT) is a traditional Chinese medicine reported to have a variety of pharmacological properties, including anticancer properties. However, the effects of RUT on breast cancer and its underlying molecular mechanism of action remain unclear. In the present study, we observed a significant downregulation of microRNA (miR)−129-1-3p in mouse breast cancer cells (4T1) compared with the expression in mouse normal breast epithelial cells (HC11). We also found that RUT could increase the expression of miR-129-1-3p in 4T1 cells and suppress cell proliferation. To elucidate the molecular mechanism of action of RUT, miR-129-1-3p mimics and its inhibitor were transfected into 4T1 cells. miR-129-1-3p overexpression could inhibit the proliferation, invasion, migration, and calcium overload of mouse breast cancer cells and also enhance apoptosis, whereas miR-129-1-3p knockdown had the opposite effects. Taken together, cell-based experiments indicated that RUT restrains the growth of mouse breast cancer cells by regulating the miR-129-1-3p/Ca 2+ signaling pathway. This study also revealed the inhibitory effect of RUT on breast cancer cells at the noncoding RNA level and provided a theoretical foundation for the application of RUT as a drug to inhibit tumor growth.

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Molecularly Stratified Treatment Options in Primary Refractory DLBCL/HGBL with MYC and BCL2 or BCL6 Rearrangements (HGBL, NOS with MYC/BCL6)

Witte¹,

Riedl²,

Künstner³

et al. 2023

Targ Oncol

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Background There is growing evidence supporting multidisciplinary molecular tumor boards (MTB) in solid tumors whereas hematologic malignancies remain underrepresented in this regard. Objective The present study aimed to assess the clinical relevance of MTBs in primary refractory diffuse large B-cell lymphomas/high-grade B-cell lymphomas with MYC and BCL2 rearrangements (prDLBCL/HGBL- MYC/BCL2 ) ( n = 13) and HGBL, not otherwise specified (NOS), with MYC and BCL6 rearrangements (prHGBL, NOS- MYC/BCL6 ) ( n = 6) based on our previously published whole-exome sequencing (WES) cohort. Patients and Methods For genomic analysis, the institutional MTB WES pipeline (University Cancer Center Schleswig-Holstein: UCCSH), certified for routine clinical diagnostics, was employed and supplemented by a comprehensive immunohistochemical work-up. Consecutive database research and annotation according to established evidence levels for molecularly stratified therapies was performed (NCT-DKTK/ESCAT). Results Molecularly tailored treatment options with NCT-DKTK evidence level of at least m2A were identified in each case. We classified mutations in accordance with biomarker/treatment baskets and detected a heterogeneous spectrum of targetable alterations affecting immune evasion (IE; n = 30), B-cell targets (BCT; n = 26), DNA damage repair (DDR; n = 20), tyrosine kinases (TK; n = 13), cell cycle (CC; n = 7), PI3K-MTOR-AKT pathway (PAM; n = 2), RAF-MEK-ERK cascade (RME; n = 1), and others (OTH; n = 11). Conclusion Our virtual MTB approach identified potential molecularly targeted treatment options alongside targetable genomic signatures for both prDLBCL/HGBL- MYC/BCL2 and prHGBL, NOS- MYC/BCL6 . These results underline the potential of MTB consultations in difficult-to-treat lymphomas early in the treatment sequence. Supplementary Information The online version contains supplementary material available at 10.1007/s11523-023-00983-5.

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A systems medicine approach for finding target proteins affecting treatment outcomes in patients with non-Hodgkin lymphoma

Cited by 11 publications

References 148 publications

A systems medicine approach reveals disordered immune system and lipid metabolism in multiple sclerosis patients

A systems medicine approach reveals disordered immune system and lipid metabolism in multiple sclerosis patients

Rutin restrains the growth and metastasis of mouse breast cancer cells by regulating the microRNA‐129‐1‐3p‐mediated calcium signaling pathway

Molecularly Stratified Treatment Options in Primary Refractory DLBCL/HGBL with MYC and BCL2 or BCL6 Rearrangements (HGBL, NOS with MYC/BCL6)

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