Molecular drivers and cells of origin in pancreatic ductal adenocarcinoma and pancreatic neuroendocrine carcinoma
AbstractPancreatic cancer is one of the most common causes of cancer-related deaths worldwide. The two major histological subtypes of pancreatic cancer are pancreatic ductal adenocarcinoma (PDAC), accounting for 90% of all cases, and pancreatic neuroendocrine neoplasm (PanNEN), which makes up 3 –5% of all cases. PanNEN is classified into well-differentiated pancreatic neuroendocrine tumor and poorly-differentiated pancreatic neuroendocrine carcinoma (PanNEC). Although PDAC and PanNEN are commonly thought to be different diseases with distinct biology, cell of origin, and genomic abnormal ities, the idea that PDAC and...
Source: Experimental Hematology and Oncology - October 22, 2020 Category: Cancer & Oncology Source Type: research

The global, regional, and national burden of kidney cancer and attributable risk factor analysis from 1990 to 2017
ConclusionsGenerally, from 1990 to 2017, the incidence rate in developed countries had gone down from the historic peak values while the incidence rate was still on the rise in developing counties. Given the aging trend in the globe, it is necessary to appeal to the public to decrease the exposure of kidney cancer-associated risk factors. (Source: Experimental Hematology and Oncology)
Source: Experimental Hematology and Oncology - September 28, 2020 Category: Cancer & Oncology Source Type: research

Expression differences of miR-142-5p between treatment-na ïve chronic myeloid leukemia patients responding and non-responding to imatinib therapy suggest a link to oncogenic ABL2, SRI, cKIT and MCL1 signaling pathways critical for development of therapy resistance
ConclusionMiR-142-5p and to a certain extend also miR-365a-3p were able to discriminate treatment-na ïve CML patients not responding to imatinib in the course of their treatment from patients, who responded to therapy. However, further large-scale studies should clarify if the identified miRNAs have the potential as predictive biomarkers for TKI resistance. (Source: Experimental Hematology and Oncology)
Source: Experimental Hematology and Oncology - September 25, 2020 Category: Cancer & Oncology Source Type: research

miR-100 inhibits cell proliferation in mantle cell lymphoma by targeting mTOR
AbstractBackgroundmiR-100 is reported to be associated with cell proliferation and apoptosis. However, the function of miR-100 in mantle cell lymphoma (MCL) is unknown. The purpose of this study is to analyze the abnormal expression of miR-100 and mTOR in MCL together with their potential biological function and pathogenesis.MethodEighteen MCL tissue samples and 3 cell lines (Jeko-1, Mino, Granta-519) were investigated in this research study, while eighteen samples of proliferative lymphadenitis from patients and peripheral lymphocyte cells from healthy volunteers served as controls. The expression and alteration of miR-10...
Source: Experimental Hematology and Oncology - September 25, 2020 Category: Cancer & Oncology Source Type: research

Frontiers in the COVID-19 vaccines development
AbstractNovel corona virus caused pneumonia first reported in December, 2019 in Wuhan, China was later named COVID-19. Due to its special pathogenicity, COVID-19 transmitted with high speed beyond borders and has significantly affected normal life. Currently, no specific drugs, treatment or vaccines are available. Vaccine development for COVID-19 is a highly complex process involving viral genomic studies, identification of target for vaccine, vaccine design, manufacturing, storage and distribution, preclinical and clinical safety and efficacy studies. The high levels of efforts and global collaboration at this scale is un...
Source: Experimental Hematology and Oncology - September 2, 2020 Category: Cancer & Oncology Source Type: research

Effects of decitabine on allogeneic immune reactions of donor lymphocyte infusion via activation of dendritic cells
ConclusionsOur results suggest that DEC primes allogeneic immune reactions of DLI via DC activation, and GVHD and GVL effects are separable through optimal DLI timing based on DEC-induced increase in IFN- γ expression levels. (Source: Experimental Hematology and Oncology)
Source: Experimental Hematology and Oncology - September 2, 2020 Category: Cancer & Oncology Source Type: research

Regulation of metabolic reprogramming by tumor suppressor genes in pancreatic cancer
ConclusionAbnormal metabolism and genetic mutations are mutually causal and complementary in tumor initiation and development. A clear understanding of how metabolic reprogramming is regulated by the mutated genes would provide important insights into the pathogenesis and ultimately treatment of pancreatic cancer. (Source: Experimental Hematology and Oncology)
Source: Experimental Hematology and Oncology - September 2, 2020 Category: Cancer & Oncology Source Type: research

Risk factors and outcome of COVID-19 in patients with hematological malignancies
AbstractBackgroundPrognostic factors of poor outcome in patients with hematological malignancies and COVID-19 are poorly defined.Patients and methodsThis was a Spanish transplant group and cell therapy (GETH) multicenter retrospective observational study, which included a large cohort of blood cancer patients with laboratory-confirmed SARS-CoV-2 infection through PCR assays from March 1st 2020 to May 15th 2020.ResultsWe included 367 pediatric and adult patients with hematological malignancies, including recipients of autologous (ASCT) (n  = 58) or allogeneic stem cell transplantation (allo-SCT) (n =&th...
Source: Experimental Hematology and Oncology - August 24, 2020 Category: Cancer & Oncology Source Type: research

Two-year long safety and efficacy of deferasirox film-coated tablets in patients with thalassemia or lower/intermediate risk MDS: phase 3 results from a subset of patients previously treated with deferasirox in the ECLIPSE study
ConclusionsThe results from this 2-year interventional study suggest that the recommended dosing of deferasirox FCT, with better tolerability, palatability, and compliance, offers a favorable option of ICT for long-term management of iron overload and associated complications in TDT.Trial registration ClinicalTrials.gov, NCT02720536. Registered 28 March 2016,https://www.clinicaltrials.gov/ct2/show/NCT02720536 (Source: Experimental Hematology and Oncology)
Source: Experimental Hematology and Oncology - August 9, 2020 Category: Cancer & Oncology Source Type: research

Primary chemoradiation with cisplatin versus cetuximab for locally advanced head and neck cancer: a retrospective cohort study
ConclusionHPV/p16-positive and smoking cohorts treated with cisplatin-based chemoradiotherapy had a significantly better OS versus cetuximab. (Source: Experimental Hematology and Oncology)
Source: Experimental Hematology and Oncology - August 4, 2020 Category: Cancer & Oncology Source Type: research

The frequency and inter-relationship of PD-L1 expression and tumour mutational burden across multiple types of advanced solid tumours in China
ConclusionsOur results showed the PD-L1 expression status and TMB in various types of advanced solid tumours in Chinese patients and their relationships with PD-1+ Tils and CD8+ T cell infiltration, which may inform ICI treatment. (Source: Experimental Hematology and Oncology)
Source: Experimental Hematology and Oncology - August 2, 2020 Category: Cancer & Oncology Source Type: research

Pancreatic cancer resistance conferred by stellate cells: looking for new preclinical models
AbstractPancreatic ductal adenocarcinoma (PDAC) has an extremely poor response to chemo- and (modest-dose conventionally fractionated) radio-therapy. Emerging evidence suggests that pancreatic stellate cells (PSCs) secrete deoxycytidine, which confers resistance to gemcitabine. In particular, deoxycytidine was detected by analysis of metabolites in fractionated media from different mouse PSCs, showing that it caused PDAC cells chemoresistance by reducing the capacity of deoxycytidine kinase (dCK) for gemcitabine phosphorylation. However, data on human models are missing and dCK expression was not associated with clinical e...
Source: Experimental Hematology and Oncology - August 2, 2020 Category: Cancer & Oncology Source Type: research

SARS-CoV-2 induced thrombocytopenia as an important biomarker significantly correlated with abnormal coagulation function, increased intravascular blood clot risk and mortality in COVID-19 patients
ConclusionsLow platelet count is associated with abnormal coagulation function and increased risk of DIC, severe disease manifestation and increased mortality in patients with COVID-19. (Source: Experimental Hematology and Oncology)
Source: Experimental Hematology and Oncology - July 16, 2020 Category: Cancer & Oncology Source Type: research

Macrophage, the potential key mediator in CAR-T related CRS
AbstractChimeric antigen receptor (CAR) T cell therapy is a new frontier in cancer therapy. The toxicity of cytokine release syndrome (CRS) has become one of the major challenges that limits the wider use of CAR T cells to fight cancer. Exploration of CRS pathogenesis and treatment is becoming the main focus of ongoing studies. Myeloid-derived macrophages were found to play a critical role in CRS pathogenesis, and these cells mediate the major production of core cytokines, including IL-6, IL-1 and interferon (IFN)- γ. Colocalization of macrophages and CAR T cells was also identified as necessary for inducing CRS, and...
Source: Experimental Hematology and Oncology - July 9, 2020 Category: Cancer & Oncology Source Type: research

Leukemia incidence trends at the global, regional, and national level between 1990 and 2017
ConclusionsA significant decrease in leukemia incidence was observed between 1990 and 2017. However, in the same period, the incidence rates of AML and CLL significantly increased in most countries, suggesting that both types of leukemia might become a major global public health concern. (Source: Experimental Hematology and Oncology)
Source: Experimental Hematology and Oncology - June 18, 2020 Category: Cancer & Oncology Source Type: research

RDGN-based predictive model for the prognosis of breast cancer
ConclusionThis study showed that aberrant RDGN expression was an unfavorable factor for breast cancer. This RDGN-based comprehensively framework was meaningful for predicting the prognosis of breast cancer patients. (Source: Experimental Hematology and Oncology)
Source: Experimental Hematology and Oncology - June 14, 2020 Category: Cancer & Oncology Source Type: research

Development of human prostate cancer stem cells involves epigenomic alteration and PI3K/AKT pathway activation
AbstractBackgroundHuman prostate cancer spheres endowed with stem cell properties have been obtained from androgen-dependent cell line LNCaP after exposure to an epigenomic modulator phenethyl isothiocynate (PEITC). Sphere cells can self-renew and grow with androgen, and also without androgen. Little is known about the signaling pathway and mechanism in the development of the stem cells in the spheres.MethodsExpression of phosphoinositol-3 kinase (PI3K) pathway members and histone acetylation were quantified in the tumor spheres and LNCaP cells by western immunoblotting.ResultsThe level of phosphorylated AKT was significan...
Source: Experimental Hematology and Oncology - June 10, 2020 Category: Cancer & Oncology Source Type: research

Interleukin-6-knockdown of chimeric antigen receptor-modified T cells significantly reduces IL-6 release from monocytes
ConclusionCAR T-derived IL-6 is one of the most important initiators to amplify release of IL-6 from monocytes that further drive sCRS development. IL-6 knockdown in ssCART-19 cells by shRNA technology provide a promising strategy to improve the safety of CAR T cell therapy. (Source: Experimental Hematology and Oncology)
Source: Experimental Hematology and Oncology - June 7, 2020 Category: Cancer & Oncology Source Type: research

Microenvironment characterization and multi-omics signatures related to prognosis and immunotherapy response of hepatocellular carcinoma
ConclusionsOur work demonstrated 3 immune clusters with different features. More importantly, multi-omics signatures, such as MMP9 was identified based on three clusters to help us recognize patients with different prognosis and responses to immunotherapy in HCC. This study could further reveal the immune status of HCC and provide potential predictors for immune checkpoint treatment response. (Source: Experimental Hematology and Oncology)
Source: Experimental Hematology and Oncology - May 24, 2020 Category: Cancer & Oncology Source Type: research

The effects of B cell depletion on immune related adverse events associated with immune checkpoint inhibition
AbstractThis letter describes the potential effect of B cell depletion on immune related adverse events associated with immune checkpoint inhibition. B cell depleting agents such as rituximab reduce B cell to plasma cell differentiation and antibody production. This treatment strategy is used in several immune mediated inflammatory diseases such as rheumatoid arthritis and small vessel vasculitis. The immune related adverse events associated with immune checkpoint inhibition resemble immune mediated inflammatory diseases. Here, we report a lower incidence of hypothyroidism in a trial of combined B cell depletion and immune...
Source: Experimental Hematology and Oncology - May 24, 2020 Category: Cancer & Oncology Source Type: research

Frequent upregulation of G9a promotes RelB-dependent proliferation and survival in multiple myeloma
ConclusionsIn this study, we demonstrated that G9a is upregulated in most multiple myeloma cell lines. Furthermore, G9a loss-of-function analysis provided evidence that G9a contributes to multiple myeloma cell survival and proliferation. This study found that G9a interacts with NF- κB pathway as a key regulator of RelB in multiple myeloma and regulates RelB-dependent multiple myeloma survival. G9a therefore is a promising therapeutic target for multiple myeloma. (Source: Experimental Hematology and Oncology)
Source: Experimental Hematology and Oncology - May 21, 2020 Category: Cancer & Oncology Source Type: research

Dual EGFR blockade with cetuximab and erlotinib combined with anti-VEGF antibody bevacizumab in advanced solid tumors: a phase 1 dose escalation triplet combination trial
ConclusionsThe triplet combination of erlotinib, cetuximab, and bevacizumab was well tolerated, conferring clinical benefit in heavily pretreated patients. Future studies are warranted with second or third-generation EGFR tyrosine kinase triplet combinations in the EGFR pathway aberrant patients.Trial Registration: ClinicalTrials.gov Identifier: NCT00543504. Sponsor(s): National Cancer Institute (NCI), MD Anderson Cancer Center (Source: Experimental Hematology and Oncology)
Source: Experimental Hematology and Oncology - April 19, 2020 Category: Cancer & Oncology Source Type: research

Efficacy and safety of rituximab in autoimmune and microangiopathic hemolytic anemia: a systematic review and meta-analysis
ConclusionRTX is more effective than the treatments without RTX for AIHA and MAHA and is well-tolerated. (Source: Experimental Hematology and Oncology)
Source: Experimental Hematology and Oncology - April 14, 2020 Category: Cancer & Oncology Source Type: research

Alternative donor peripheral blood stem cell transplantation for the treatment of high-risk refractory and/or relapsed childhood acute leukemia: a randomized trial
AbstractBackgroundThe high-risk refractory and/or relapsed (R/R) childhood acute leukemia prognosis is poor, and allogeneic stem cell transplantation (allo-HSCT) is the most prudent treatment modality. However, there are limited matched sibling donors (MSDs), and alternative donors (ADs) are the main source for allo-HSCT. Thus, we evaluated the clinical efficacy of AD peripheral allo-HSCT for treating high-risk R/R childhood acute leukemia.MethodsWe assessed 111 children who underwent allo-HSCT at the Affiliated Cancer Hospital of Zhengzhou University between October 2006 and July 2019. The patients were divided in the MSD...
Source: Experimental Hematology and Oncology - April 5, 2020 Category: Cancer & Oncology Source Type: research

Clinical implications of recurrent gene mutations in acute myeloid leukemia
AbstractAcute myeloid leukemia (AML) is a genetically heterogeneous clonal malignancy characterized by recurrent gene mutations. Genomic heterogeneity, patients ’ individual variability, and recurrent gene mutations are the major obstacles among many factors that impact treatment efficacy of the AML patients. With the application of cost- and time-effective next-generation sequencing (NGS) technologies, an enormous diversity of genetic mutations has been identified. The recurrent gene mutations and their important roles in acute myeloid leukemia (AML) pathogenesis have been studied extensively. In this review, we sum...
Source: Experimental Hematology and Oncology - March 26, 2020 Category: Cancer & Oncology Source Type: research

Indirect comparison of azacitidine and decitabine for the therapy of elderly patients with acute myeloid leukemia: a systematic review and network meta-analysis
ConclusionsCompared to CCR, decitabine and azacitidine can promote studied outcomes in elderly AML patients. Indirect evidence with low certainty was used to compare these two agents. The superiority of either agent cannot be confirmed, and head-to-head clinical trials are still required. (Source: Experimental Hematology and Oncology)
Source: Experimental Hematology and Oncology - March 15, 2020 Category: Cancer & Oncology Source Type: research

Gene mutational analysis by NGS and its clinical significance in patients with myelodysplastic syndrome and acute myeloid leukemia
ConclusionsDifferent gene mutations had been found in majority of MDS and AML patients. MDS and AML patients had different gene mutation patterns. AML patients with fewer or no gene mutations had a better chance of achieving CR when treated with IA and DA regimen induction chemotherapy. (Source: Experimental Hematology and Oncology)
Source: Experimental Hematology and Oncology - January 5, 2020 Category: Cancer & Oncology Source Type: research

The SMAC mimetic LCL-161 selectively targets JAK2 V617F mutant cells
ConclusionLCL-161 may be therapeutically useful in MPN, in particular when exogenous TNF α signaling is blocked. NFĸB activation is a characteristic feature of JAK2V617F mutant cells and this sensitizes them to SMAC mimetic induced killing even in the absence of TNF α. However, when exogenous TNFα is added, NFĸB is activated in both mutant and wild-type cells, abolishing the differential sensitivity. Moreover, JAK kinase activity is required for the differential sensitivity of JAK2V617F mutant cells, suggesting that the addition of JAK2 inhibitors to SMAC mimetics would detract from the ability of SMAC ...
Source: Experimental Hematology and Oncology - January 1, 2020 Category: Cancer & Oncology Source Type: research

Immune pressures drive the promoter hypermethylation of neoantigen genes
AbstractCancer cells with strong immunogenicity are susceptible for elimination by cancer immunoediting, while the subpopulations with weak immunogenicity survive. As a result, a subset of cancer cells evade the immune attack and evolve into overt clinical lesions. During cancer evolution, it has been well established that multiple alterations such as the dysfunction of antigen presentation machinery and the upregulation of immunosuppressive signals (e.g. PD-L1) play important roles in immune escape. Recently, promoter hypermethylation of neoantigen genes has been proposed to be a vital mechanism of immunoediting. This epi...
Source: Experimental Hematology and Oncology - November 28, 2019 Category: Cancer & Oncology Source Type: research

Gut microbiome and CAR-T therapy
AbstractConsiderable progress has been made in cancer therapeutics recently with targeted strategies that are efficacious and less toxic. Immunotherapy and chimeric antigen receptor (CAR) T-cells are increasingly being evaluated in a variety of tumors in the relapsed/refractory as well as frontline disease settings, predominantly in hematologic malignancies (HM). Despite impressive outcomes in select patients, there remains significant heterogeneity in clinical response to CAR T-cells. The gut microbiome has emerged as one of the key host factors that could potentially be modulated to enhance responses to immunotherapy. Se...
Source: Experimental Hematology and Oncology - November 18, 2019 Category: Cancer & Oncology Source Type: research

A high-throughput screening identifies histone deacetylase inhibitors as therapeutic agents against medulloblastoma
ConclusionsOur findings suggest that histone deacetylase inhibitors are potent therapeutic agents against medulloblastoma. (Source: Experimental Hematology and Oncology)
Source: Experimental Hematology and Oncology - November 14, 2019 Category: Cancer & Oncology Source Type: research

Advances and perspectives of PARP inhibitors
AbstractDNA damage repair deficiency leads to the increased risk of genome instability and oncogenic transformation. In the meanwhile, this deficiency could be exploited for cancer treatment by inducing excessive genome instability and catastrophic DNA damage. Continuous DNA replication in cancer cells leads to higher demand of DNA repair components. Due to the oncogenic loss of some DNA repair effectors (e.g. BRCA) and incomplete DNA repair repertoire, some cancer cells are addicted to certain DNA repair pathways such as Poly (ADP-ribose) polymerase (PARP)-related single-strand break repair pathway. The interaction betwee...
Source: Experimental Hematology and Oncology - November 10, 2019 Category: Cancer & Oncology Source Type: research

Recent advances on blinatumomab for acute lymphoblastic leukemia
AbstractAlthough complete remission rate of B cell acute lymphoblastic leukemia (B-ALL) has improved significantly over the past few decades, patients with relapsed/refractory ALL still have dismal outcome. Tyrosine kinase inhibitors, antibody –drug conjugates and chimeric antigen receptor T cell therapy are changing the therapy landscape for B- ALL. Blinatumomab, a bi-specific T cell engager, has been approved for patients with relapsed/refractory and minimal residual disease positive B-ALL. This review summarized data from recent clin ical trials of blinatumomab for B-ALL treatment. (Source: Experimental Hematology and Oncology)
Source: Experimental Hematology and Oncology - November 5, 2019 Category: Cancer & Oncology Source Type: research

Development of molecular and pharmacological switches for chimeric antigen receptor T cells
AbstractThe use of chimeric antigen receptor (CAR) T cell technology as a therapeutic strategy for the treatment blood-born human cancers has delivered outstanding clinical efficacy. However, this treatment modality can also be associated with serious adverse events in the form of cytokine release syndrome. While several avenues are being pursued to limit the off-target effects, it is critically important that any intervention strategy has minimal consequences on long term efficacy. A recent study published in Science Translational Medicine by Dr. Hudecek ’s group proved that dasatinib, a tyrosine kinase inhibitor, c...
Source: Experimental Hematology and Oncology - November 4, 2019 Category: Cancer & Oncology Source Type: research

The efficacy and safety of combination of PD-1 and CTLA-4 inhibitors: a meta-analysis
ConclusionCombination treatment of α-PD-1 and α-CTLA-4 is a feasible strategy with enhanced efficacy and acceptable adverse event. Moreover, for some low PD-L1 expression patients, α-CTLA-4 might decrease the risk of resistance to α-PD-1 and demonstrate the synergistic anti-tumor effect. (Source: Experimental Hematology and Oncology)
Source: Experimental Hematology and Oncology - October 24, 2019 Category: Cancer & Oncology Source Type: research

Targeted and novel therapy in advanced gastric cancer
AbstractThe systemic treatment options for advanced gastric cancer (GC) have evolved rapidly in recent years. We have reviewed the recent data of clinical trial incorporating targeted agents, including inhibitors of angiogenesis, human epidermal growth factor receptor 2 (HER2), mesenchymal –epithelial transition, epidermal growth factor receptor, mammalian target of rapamycin, claudin-18.2, programmed death-1 and DNA. Addition of trastuzumab to platinum-based chemotherapy has become standard of care as front-line therapy in advanced GC overexpressing HER2. In the second-line setting , ramucirumab with paclitaxel sign...
Source: Experimental Hematology and Oncology - October 10, 2019 Category: Cancer & Oncology Source Type: research

Identification of osimertinib-resistant EGFR L792 mutations by cfDNA sequencing: oncogenic activity assessment and prevalence in large cfDNA cohort
AbstractCell-free DNA (cfDNA) next-generation sequencing has the potential to capture tumor heterogeneity and genomic evolution under treatment pressure in a non-invasive manner. Here, we report the detection ofEGFR L792 mutations, a non-covalent mechanism of osimertinib resistance, using Guardant360 cfDNA testing in a patient with metastaticEGFR-mutant non-small cell lung cancer (NSCLC) whose disease progressed on osimertinib. We subsequently analyzed a large cohort of over 1800 additional patient samples harboring anEGFR T790M mutation and identified a concomitant L792 mutation in a total of 22 (1.2%) cases. In vitro fun...
Source: Experimental Hematology and Oncology - October 10, 2019 Category: Cancer & Oncology Source Type: research

LY86, LRG1 and PDE9A genes overexpression in umbilical cord blood hematopoietic stem progenitor cells by acute myeloid leukemia (M3) microvesicles
ConclusionOur results suggest that healthy HSPCs can be transformed genetically by leukemia microvesicles to over express LSC specific genes. This may be further evidence of leukemia-like transformation by leukemia microvesicles. (Source: Experimental Hematology and Oncology)
Source: Experimental Hematology and Oncology - September 17, 2019 Category: Cancer & Oncology Source Type: research

Role of some members of chemokine/cytokine network in the pathogenesis of thalassemia and sickle cell hemoglobinopathies: a mini review
AbstractThe word of hemoglobinopathy is described for an array of disorders that affecting hemoglobin (Hb) functions. Hb is a molecule with 68  kDa molecular weight, serving as oxygen carrying metalloprotein. Hemoglobinopathy includes a wide range of Hb structural deficits varying from thalassemia to sickle cell disease. Cyto-chemokine network members are pivotally involved in the pathogenesis of hemoglobinopathies, however, the exact rol e of these mediators in the development of these disorders yet to be well addressed. Cytokines and chemokines are generated by inflamed endothelial cells that promote the expression ...
Source: Experimental Hematology and Oncology - September 10, 2019 Category: Cancer & Oncology Source Type: research

Cabozantinib and apixaban: an hitherto unreported interaction
We describe, for the first time, a case of neutropenia and thrombocytopenia in a patient in treatment with cabozantinib, a novel anticancer treatment used in metastatic renal cell carcinoma, and apixaban with promptly resumption of the toxicity after the interruption of cabozantinib. This case suggest a possible interaction between these two pharmaceutical agents, which merit caution considering the spreading of the two drugs. (Source: Experimental Hematology and Oncology)
Source: Experimental Hematology and Oncology - September 10, 2019 Category: Cancer & Oncology Source Type: research

Autoimmune rhabdomyolysis and a multiorgan display of PD-1 inhibitor induced immune related adverse events during treatment of metastatic melanoma
ConclusionsPD-1 inhibitors are now widely used in a multitude of cancer types including melanoma, advanced non-small cell lung cancer, metastatic renal cell carcinoma, and Hodgkin lymphoma amongst others. While these agents are often well tolerated, they are associated with a unique profile of immune-related toxicities that can cause significant morbidity and mortality. Education of both patients and healthcare providers is essential for diagnosis and treatment of these adverse events early in their course. This case highlights the uncommon but potentially serious PD-1-associated toxicity of myopathy and rhabdomyolysis alo...
Source: Experimental Hematology and Oncology - September 9, 2019 Category: Cancer & Oncology Source Type: research

Achievements and futures of immune checkpoint inhibitors in non-small cell lung cancer
AbstractNon-small cell lung cancer (NSCLC) has been threatening human health for years. Cytotoxicity-based chemotherapy seems to reach plateau in NSCLC treatment. Immunotherapy with immune checkpoint inhibitors (ICIs) against programmed cell death 1 (PD-1/L1) axis are to provide long-term survival benefits for wild-type advanced NSCLC patients with acceptable adverse effects. Though beneficiary population is limited from monotherapy, combination strategies are expanding indicators. Retrospective evidences suggested ICIs are also potentially useful for brain metastasis. Furthermore, the combination of ICIs and surgery are t...
Source: Experimental Hematology and Oncology - August 21, 2019 Category: Cancer & Oncology Source Type: research

A novel RNA variant of human concentrative nucleoside transporter 1 (hCNT1) that is a potential cancer biomarker
ConclusionWe have identified a novel intron retaining and exon skipping splice variant of the hCNT1  nucleoside transporter, and designated it hCNT1-IR, which has a similar tissue expression distribution as the normal hCNT1 variant, but unlike the normal transcript, hCNT1-IR is overexpressed in some cancers and may serve as a potential cancer biomarker. (Source: Experimental Hematology and Oncology)
Source: Experimental Hematology and Oncology - August 21, 2019 Category: Cancer & Oncology Source Type: research

Analysis of TET2 mutations in paroxysmal nocturnal hemoglobinuria (PNH)
ConclusionsWe conclude that mutations inTET2 may contribute to clonal expansion in exceptional cases of PNH. (Source: Experimental Hematology and Oncology)
Source: Experimental Hematology and Oncology - August 20, 2019 Category: Cancer & Oncology Source Type: research

Frontline therapies for untreated chronic lymphoid leukemia
AbstractTherapy for chronic myeloid leukemia (CLL) is going through a major paradigm shift. Combination chemoimmunotherapy regimens have been the frontline therapies for CLL, whereas chlorambucil remained the standard frontline therapy for older patients (65  years or older) with CLL until recently. Monoclonal antibodies including rituximab, ofatumumab and obinutuzumab have been used for CLL therapy. Novel immunotherapeutics with chimeric antigen receptor (CAR) engineered T cells is rapidly migrating to clinical applications. Targeted therapies with sm all molecule inhibitors against Bruton tyrosine kinase (BTK) such ...
Source: Experimental Hematology and Oncology - August 16, 2019 Category: Cancer & Oncology Source Type: research

Ibrutinib inhibits antibody dependent cellular cytotoxicity induced by rituximab or obinutuzumab in MCL cell lines, not overcome by addition of lenalidomide
ConclusionIbrutinib negatively affects anti-CD20 induced cell death in MCL, not reversed by lenalidomide. Explorations of sequential administration and selective BTK-inhibitors may reveal the optimal combination of novel agents in MCL. (Source: Experimental Hematology and Oncology)
Source: Experimental Hematology and Oncology - August 5, 2019 Category: Cancer & Oncology Source Type: research

Healthcare cost comparison analysis of nivolumab in combination with ipilimumab versus nivolumab monotherapy and ipilimumab monotherapy in advanced melanoma
ConclusionsThe total costs incurred by a patient over a 48-month period following treatment initiation with NIVO  + IPI are lower when compared with patients initiating monotherapies; further, the cost advantage is seen to be increasing over time. The clinical benefits offered by the regimen are thus supplemented by a cost advantage, as patients receiving either monotherapy treatment experience faster prog ression and, consequently, higher subsequent treatment costs. (Note: The cost results reported here are specific to the UK, and Germany, and may not be generalizable to other geographies). (Source: Experime...
Source: Experimental Hematology and Oncology - July 2, 2019 Category: Cancer & Oncology Source Type: research

An expanded biomarker panel for the detection of prostate cancer from urine DNA
ConclusionsThis study shows that large marker panels can be analyzed from urine DNA without loss of sensitivity or specificity. Using 32 markers improved the stratification of patients undergoing screening for PCA particularly for patients below the 10of32 threshold. The results show the utility of larger biomarker panels for PCA diagnosis and suggest that the development of the panels needed to monitor disease progression could be successfully accomplished. (Source: Experimental Hematology and Oncology)
Source: Experimental Hematology and Oncology - June 26, 2019 Category: Cancer & Oncology Source Type: research

Novel GTF2I – PDGFRB and IKZF1 – TYW1 fusions in pediatric leukemia with normal karyotype
ConclusionsThe examined pediatric leukemia is a Ph-like ALL which carries novelGTF2I–PDGFRB andIKZF1–TYW1 fusion genes together with additional submicroscopic deletions. Because hematologic neoplasms withPDGFRB-fusion genes can be treated with tyrosine kinase inhibitors, the detection of such novel fusions may be clinically important. Since theGTF2I–PDGFRB could be detected only after molecular studies of the leukemic cells, further investigations of ALL-cases, perhaps especially but not exclusively with a normal karyotype, are needed in order to determine the frequency ofGTF2I–PDGFRB in leukemia, a...
Source: Experimental Hematology and Oncology - May 28, 2019 Category: Cancer & Oncology Source Type: research

NRAS and KRAS polymorphisms are not associated with hepatoblastoma susceptibility in Chinese children
ConclusionsThe data suggest thatNRAS andKRAS polymorphisms are irrelevant to hepatoblastoma susceptibility among Chinese population. (Source: Experimental Hematology and Oncology)
Source: Experimental Hematology and Oncology - May 8, 2019 Category: Cancer & Oncology Source Type: research