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International Journal of Oncology Jan 2018Annexin A2 is a 36-kDa protein interfering with multiple cellular processes especially in cancer progression. The present review aimed to show the relations between... (Review)
Review
Annexin A2 is a 36-kDa protein interfering with multiple cellular processes especially in cancer progression. The present review aimed to show the relations between Annexin A2 and cancer. A systematic search for studies investigating cancer and Annexin A2 expression was conducted using PubMed. Acute lymphoblastic leukaemia, acute promyelocytic leukaemia, clear cell renal cell carcinoma, breast, cervical, colorectal, endometrial, gastric cancer, glioblastoma, hepatocellular carcinoma, lung, multiple myeloma, oesophageal squamous cell carcinoma, ovarian cancer, pancreatic duct adenocarcinoma, prostate cancer and urothelial carcinoma were evaluated. Annexin A2 expression correlates with resistance to treatment, binding to the bone marrow, histological grade and type, TNM-stage and shortened overall survival. The regulation of Annexin A2 is of interest due to its potential as target for a more individualized cancer management.
Topics: Animals; Annexin A2; Biomarkers, Tumor; Humans; Neoplasms
PubMed: 29115416
DOI: 10.3892/ijo.2017.4197 -
Seminars in Thrombosis and Hemostasis Jul 2021Bleeding and thrombosis are well-known complications to hematological malignancies, and changes in fibrinolysis impact both these issues. In the present systematic...
Bleeding and thrombosis are well-known complications to hematological malignancies, and changes in fibrinolysis impact both these issues. In the present systematic review, we provide an overview and discussion of the current literature in regards to clinical manifestations, diagnosis, and treatment of altered fibrinolysis in patients suffering from hematological malignancies, beyond acute promyelocytic leukemia. We performed a systematic literature search employing the databases Pubmed, Embase, and Web of Science to identify original studies investigating fibrinolysis in hematological malignancies. Studies investigating fibrinolysis in acute promyelocytic leukemia or disseminated intravascular coagulation were excluded. We identified 32 studies fulfilling the inclusion criteria. A majority of the studies were published more than two decades ago, and none of the studies examined all available markers of fibrinolysis or used dynamic clot lysis assays. In acute leukemia L-asparaginase treatment induced a hypofibrinolytic state, and prior to chemotherapy there seemed to be little to no change in fibrinolysis. In studies examining fibrinolysis during chemotherapy results were ambiguous. Two studies examining multiple myeloma indicated hypofibrinolysis prior to chemotherapy, and in another plasma cell disease, amyloid light chain-amyloidosis, clear signs of hyperfibrinolysis were demonstrated. In myeloproliferative neoplasms, the studies reported signs of hypofibrinolysis, in line with the increased risk of thrombosis in this disease. Only one study regarding lymphoma was identified, which indicated no alterations in fibrinolysis. In conclusion, this systematic review demonstrated that only sparse, and mainly old, evidence exists on fibrinolysis in hematological malignancy. However, the published studies showed a tendency toward hypofibrinolysis in myeloproliferative disorders, an increased risk of hyperfibrinolysis, and bleeding in patients with AL-amyloidosis, whereas studies regarding acute leukemias were inconclusive except with regard to L-asparaginase treatment, which induced a hypofibrinolytic state.
Topics: Amyloidosis; Asparaginase; Blood Coagulation Disorders; Fibrinolysis; Hematologic Neoplasms; Hemorrhage; Humans; Leukemia, Promyelocytic, Acute; Thrombosis
PubMed: 34058766
DOI: 10.1055/s-0041-1725099 -
Cancers May 2020It has been suggested that 1-2% of acute promyelocytic leukemia (APL) patients present variant rearrangements of retinoic acid receptor alpha (RARα) fusion gene, with... (Review)
Review
It has been suggested that 1-2% of acute promyelocytic leukemia (APL) patients present variant rearrangements of retinoic acid receptor alpha (RARα) fusion gene, with the promyelocytic leukaemia zinc finger (PLZF)/RAR being the most frequent. Resistance to all-trans-retinoic acid (ATRA) and arsenic trioxide (ATO) has been suggested in PLZF/RAR and other variant APLs. Herein, we analyze the incidence, characteristics, and outcomes of variant APLs reported to the multinational PETHEMA (Programa para el Tratamiento de Hemopatias Malignas) registry, and we perform a systematic review in order to shed light on strategies to improve management of these extremely rare diseases. Of 2895 patients with genetically confirmed APL in the PETHEMA registry, 11 had variant APL (0.4%) (9 PLZF-RAR and 2 NPM1-RAR), 9 were men, with median age of 44.6 years (3 months to 76 years), median leucocytes (WBC) 16.8 × 10/L, and frequent coagulopathy. Eight patients were treated with ATRA plus chemotherapy-based regimens, and 3 with chemotherapy-based. As compared to previous reports, complete remission and survival was slightly better in our cohort, with 73% complete remission (CR) and 73% survival despite a high relapse rate (43%). After analyzing our series and performing a comprehensive and critical review of the literature, strong recommendations on appropriate management of variant APL are not possible due to the low number and heterogeneity of patients reported so far.
PubMed: 32455804
DOI: 10.3390/cancers12051313 -
Frontiers in Pharmacology 2022Cancers are a potential cause of death worldwide and represent a massive burden for healthcare systems. Treating cancers requires substantial resources, including...
Cancers are a potential cause of death worldwide and represent a massive burden for healthcare systems. Treating cancers requires substantial resources, including skilled personnel, medications, instruments, and funds. Thus, developing cancer prevention and treatment measures is necessary for healthcare personnel and patients alike. (Polygonaceae family) is a plant used as a culinary ingredient. It exhibits several pharmacological activities, such as antibacterial, antifungal, antioxidant, anti-inflammatory, and anticancer. Several classes of phytochemical constituents of have been reported. The important ones might be polyphenol and flavonoid derivatives. In this systematic review, the activities of against cancerous cells were determined and summarized. Data were obtained through a systematic search of electronic databases (EMBASE, PubMed, Scopus, Thai Thesis Database, Science Direct and Clinical Key). Eight studies met the eligibility criteria. The cancerous cell lines used in the studies were lymphoma, leukemia, oral, lung, breast, colon, and liver cancer cells. Based on this review, extracts significantly affected Epstein-Barr virus (EBV) genome-carrying human lymphoblastoid (Raji), mouse lymphocytic leukemia (P388), human acute lymphocytic leukemia (Jurkat), breast adenocarcinoma (MCF-7), human colon adenocarcinoma (HT-29), human T lymphoblast (MOLT-4), human promyelocytic leukemia cell line (HL-60), human hepatocellular carcinoma (HepG2), and oral squamous cell carcinoma (SAS, SCC-9, HSC-3) through induction of cell apoptosis, arrest of the cell cycle, inhibition of cell proliferation, migration, and colonization. The molecular mechanism of against cancers was reported to involve suppressing essential proteins required for cell proliferation, colonization, migration, apoptosis, and angiogenesis. They were survivin, cyclin-D, cyclooxygenase 2 (COX-2), matrix metalloproteinase-9 (MMP-9), and vascular endothelial growth factor A (VEGF-A). The extract of was also involved in the protein kinase B (Akt)/mammalian target of rapamycin (mTOR) pathway by inhibiting the expression of Akt, phosphorylated Akt, mTOR, and phosphorylated mTOR. From the key results of this review, is a promising chemotherapy and chemopreventive agent. Further investigation of its pharmacological activity and mechanism of action should be conducted using standardized extracts. experiments and clinical trials are required to confirm the anticancer activity.
PubMed: 35571080
DOI: 10.3389/fphar.2022.875016 -
International Journal of Laboratory... Oct 2020Leukoerythroblastic reaction (LER) is characterized by the presence of immature erythroid cells and myeloid precursors (metamyelocytes, myelocytes, promyelocytes,... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND PURPOSE
Leukoerythroblastic reaction (LER) is characterized by the presence of immature erythroid cells and myeloid precursors (metamyelocytes, myelocytes, promyelocytes, myeloblasts, and blasts) as well as, exclusively in myelofibrotic disorders, teardrop cells in the peripheral blood (J Pathol Bacteriol, 42, 1936, 541; Semaine Med, 22, 1902, 373). Research on how to interpret LER and its meaning in clinical practice is scarce, and there is no consensus on the diagnostic criteria. We summarize the current evidence with the aim of clarifying the knowledge on this subject.
METHODS
We conducted a comprehensive search of the PubMed-MEDLINE, EMBASE and ELSEVIER databases, the Cochrane Library, Google Scholar, and medical journals to identify relevant papers.
RESULTS
Our search identified 425 papers, of which, 35 (11 trials and 24 case reports) ultimately met the inclusion criteria. These showed two principal groups of diseases associated with leukoerythroblastosis (LEB), corresponding to solid and hematological malignancies. The other etiologies, in order of frequency, were hemolytic diseases, infection, and others, while hemorrhage was only reported in the trials group.
CONCLUSION
The literature on LER is scarce and heterogeneous. The etiological factors of LER are diverse, and its presence in malignant disease is an indicator of disease progression and an adverse prognosis suggesting poor survival. In those cases where LER had neither hematological nor solid neoplasms, its manifestation, prognosis and its impact on our daily clinical practice are unknown.
Topics: Animals; Disease Management; Disease Susceptibility; Erythroid Cells; Humans; Leukocytes; Medical History Taking; Myeloproliferative Disorders
PubMed: 32562368
DOI: 10.1111/ijlh.13238 -
International Journal of... Apr 2020Acute promyelocytic leukemia (APL) is a subtype of acute myeloid leukemia (AML). APL is famed with some special blood coagulation disorders such as disseminated... (Review)
Review
Acute promyelocytic leukemia (APL) is a subtype of acute myeloid leukemia (AML). APL is famed with some special blood coagulation disorders such as disseminated intravascular coagulation (DIC). The therapeutic methods of APL contain All Trans Retinoic Acid (ATRA), arsenic trioxide (ATO) or/and chemotherapy. Many studies have been done on APL blood disorders and its treatment. These studies have shown different results. In this systematic article, we tried to review the effect of ATO therapy with or without ATRA and chemotherapy on DIC parameters (D-dimer, Prothrombin Time, Activated Partial Thrombin Time, Platelet count) in APL patients. The result of included studies demonstrated that although ATO can reduce the number of malignant cells in the bone marrow and peripheral blood, it does not have enough potential to attenuate the danger of high score DIC that is usual in APL patients and should be better to be used with other therapeutic methods.
PubMed: 32461798
DOI: No ID Found -
Frontiers in Genetics 2022Retinoids, natural and synthetic derivatives of vitamin A, have many regulatory functions in human body, including regulating cellular proliferation, differentiation,...
Retinoids, natural and synthetic derivatives of vitamin A, have many regulatory functions in human body, including regulating cellular proliferation, differentiation, apoptosis. Moreover, retinoids have been used successfully for the treatment of certain malignancies, especially acute promyelocytic leukemia (APL) in adults and neuroblastoma in children. However, retinoids have not yet been translated into effective systemic treatments for most solid cancers. Some recent studies have shown that retinoids promote tumorigenesis. Therefore, we performed this meta-analysis to systematically evaluate the efficacy of retinoids in the chemoprevention and treatment of cancers. We performed literature search of several electronic databases, including PubMed, Embase and Cochrane Library from 2000 January to 2021 November. Various outcomes were applied to investigate the potential of retinoids for prevention and treatment of cancers. The primary outcomes in this study were disease recurrence and clinical response. The secondary outcomes included overall survival (OS), cancer development, disease progression and event-free survival. We identified 39 randomized controlled trials with 15,627 patients in this study. Our results showed that lower recurrence rate and better clinical response were obtained in retinoids treated patients with cancer or premalignancy as compared with control. The differences were statistically significant (RR = 0.85, 95% CI = 0.74-0.96, = 0.01; RR = 1.24, 95% CI = 1.03-1.49, = 0.02, respectively). Retinoids treatment was not associated with improvement in overall survival, cancer development, disease progression or event-free survival. Subgroup analysis conducted based on cancer type showed that patients benefited from retinoids treatment in APL, renal cell carcinoma, hepatocellular carcinoma, lung cancer, Kaposi sarcoma, and complete hydatidiform mole. No significant therapeutic effect was noted in head and neck cancer, acute myeloid leukemia (AML), melanoma, breast cancer, bladder cancer, cervical intraepithelial neoplasia (CIN) or cervical carcinoma. Subgroup analysis based on tumor classification demonstrated that retinoids group obtained a lower recurrence rate and better clinical response than control group in solid cancers. In conclusion, clinical application of retinoids was associated with reduction in disease recurrence and improvement in clinical response, illustrating that retinoids play a key role in cancer prevention and therapy. Further research is needed to broaden the utility of retinoids in other types of cancers. PROSPERO, identifier CRD42022296706.
PubMed: 36437918
DOI: 10.3389/fgene.2022.1065320 -
Journal of Clinical and Diagnostic... Mar 2017Extramedullary disease, as a whole, is rare in Acute Promyelocytic Leukaemia (APML). If at all relapse occurs, following sites are involved: Central Nervous System... (Review)
Review
INTRODUCTION
Extramedullary disease, as a whole, is rare in Acute Promyelocytic Leukaemia (APML). If at all relapse occurs, following sites are involved: Central Nervous System (CNS), skin, testes, mediastinum, gingiva, and ear. Isolated CNS relapses after complete morphological and molecular remission is rarer particularly in children.
AIM
To review the literature systematically to find out the incidence of isolated CNS relapse in paediatric APML cases.
MATERIALS AND METHODS
A systematic search of major databases (Medline, Pubmed and Google Scholar) was conducted. We included all types of studies that reported about incidence or prevalence of isolated CNS relapse in children upto 18 years of age with APML.
RESULTS
A total of nine studies (with 10 cases of isolated CNS relapse) were included. Majority (70%) was high risk patients, and 60% were ≤six-year-old. Nearly, 50% were having the mean time to relapse <12 months and most (60%) of them were male. The children who died were having shorter time to CNS relapse (around 12 months), and were older (>6 to 18 years).
CONCLUSION
In the present review, disease in the high-risk group, male sex, younger age (≤six-years-old), and Promyelocytic Leukaemia/Retinoic Acid Receptor Alpha (PML-RARA) detection was found to be associated with isolated CNS relapse in children with APML. Cerebrospinal fluid (CSF) examination along with immunophenotyping and Reverse Transcription polymerase Chain Reaction (RT-PCR) for PML-RARA is required for a definite diagnosis and early treatment of patients to improve overall survival.
PubMed: 28511493
DOI: 10.7860/JCDR/2017/24196.9572 -
OncoTargets and Therapy 2014Multiple myeloma (MM) is a clonal malignancy characterized by the proliferation of malignant plasma cells in the bone marrow and the production of monoclonal... (Review)
Review
Multiple myeloma (MM) is a clonal malignancy characterized by the proliferation of malignant plasma cells in the bone marrow and the production of monoclonal immunoglobulin. Although some newly approved drugs (thalidomide, lenalidomide, and bortezomib) demonstrate significant benefit for MM patients with improved survival, all MM patients still relapse. Arsenic trioxide (ATO) is the most active single agent in acute promyelocytic leukemia, the antitumor activity of which is partly dependent on the production of reactive oxygen species. Due to its multifaceted effects observed on MM cell lines and primary myeloma cells, Phase I/II trials have been conducted in heavily pretreated patients with relapsed or refractory MM. Therapy regimens varied dramatically as to the dosage of ATO and monotherapy versus combination therapy with other agents available for the treatment of MM. Although ATO-based combination treatment was well tolerated by most patients, most trials found that ATO has limited effects on MM patients. However, since small numbers of patients were randomized to different treatment arms, trials have not been statistically powered to determine the differences in progression-free survival and overall survival among the experimental arms. Therefore, large Phase III studies of ATO-based randomized controlled trials will be needed to establish whether ATO has any potential beneficial effects in the clinical setting.
PubMed: 25246802
DOI: 10.2147/OTT.S67165 -
The Cochrane Database of Systematic... Mar 2016People with haematological disorders are frequently at risk of severe or life-threatening bleeding as a result of thrombocytopenia (reduced platelet count). This is... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
People with haematological disorders are frequently at risk of severe or life-threatening bleeding as a result of thrombocytopenia (reduced platelet count). This is despite the routine use of prophylactic platelet transfusions to prevent bleeding once the platelet count falls below a certain threshold. Platelet transfusions are not without risk and adverse events may be life-threatening. A possible adjunct to prophylactic platelet transfusions is the use of antifibrinolytics, specifically the lysine analogues tranexamic acid (TXA) and epsilon aminocaproic acid (EACA). This is an update of a Cochrane review first published in 2013.
OBJECTIVES
To determine the efficacy and safety of antifibrinolytics (lysine analogues) in preventing bleeding in people with haematological disorders.
SEARCH METHODS
We searched for randomised controlled trials (RCTs) in the Cochrane Central Register of Controlled Trials (The Cochrane Library 2016, Issue 3), MEDLINE (from 1946), Embase (from 1974), CINAHL (from 1937), the Transfusion Evidence Library (from 1950) and ongoing trial databases to 07 March 2016.
SELECTION CRITERIA
We included RCTs involving participants with haematological disorders, who would routinely require prophylactic platelet transfusions to prevent bleeding. We only included trials involving the use of the lysine analogues TXA and EACA.
DATA COLLECTION AND ANALYSIS
Two review authors independently screened all electronically-derived citations and abstracts of papers, identified by the review search strategy, for relevancy. Two review authors independently assessed the full text of all potentially relevant trials for eligibility, completed the data extraction and assessed the studies for risk of bias using The Cochrane Collaboration's 'Risk of bias' tool. We requested missing data from one author but the data were no longer available. The outcomes are reported narratively: we performed no meta-analyses because of the heterogeneity of the available data.
MAIN RESULTS
We identified three new studies in this update of the review. In total seven studies were eligible for inclusion, three were ongoing RCTs and four were completed studies. The four completed studies were included in the original review and the three ongoing studies were included in this update. We did not identify any RCTs that compared TXA with EACA.Of the four completed studies, one cross-over TXA study (eight participants) was excluded from the outcome analysis because it had very flawed study methodology. Data from the other three studies were all at unclear risk of bias due to lack of reporting of study methodology.Three studies (two TXA (12 to 56 participants), one EACA (18 participants) reported in four articles (published 1983 to 1995) were included in the narrative review. All three studies compared the drug with placebo. All three studies included adults with acute leukaemia receiving chemotherapy. One study (12 participants) only included participants with acute promyelocytic leukaemia. None of the studies included children. One of the three studies reported funding sources and this study was funded by a charity.We are uncertain whether antifibrinolytics reduce the risk of bleeding (three studies; 86 participants; very low-quality evidence). Only one study reported the number of bleeding events per participant and there was no difference in the number of bleeding events seen during induction or consolidation chemotherapy between TXA and placebo (induction; 38 participants; mean difference (MD) 1.70 bleeding events, 95% confidence interval (CI) -0.37 to 3.77: consolidation; 18 participants; MD -1.50 bleeding events, 95% CI -3.25 to 0.25; very low-quality evidence). The two other studies suggested bleeding was reduced in the antifibrinolytic study arm, but this was statistically significant in only one of these two studies.Two studies reported thromboembolism and no events occurred (68 participants, very low-quality evidence).All three studies reported a reduction in platelet transfusion usage (three studies, 86 participants; very low-quality evidence), but this was reported in different ways and no meta-analysis could be performed. No trials reported the number of platelet transfusions per participant. Only one study reported the number of platelet components per participant and there was a reduction in the number of platelet components per participant during consolidation chemotherapy but not during induction chemotherapy (consolidation; 18 participants; MD -5.60 platelet units, 95% CI -9.02 to -2.18: induction; 38 participants, MD -1.00 platelet units, 95% CI -9.11 to 7.11; very low-quality evidence).Only one study reported adverse events of TXA as an outcome measure and none occurred. One study stated side effects of EACA were minimal but no further information was provided (two studies, 74 participants, very low-quality evidence).None of the studies reported on the following pre-specified outcomes: overall mortality, adverse events of transfusion, disseminated intravascular coagulation (DIC) or quality of life (QoL).
AUTHORS' CONCLUSIONS
Our results indicate that the evidence available for the use of antifibrinolytics in haematology patients is very limited. The trials were too small to assess whether or not antifibrinolytics decrease bleeding. No trials reported the number of platelet transfusions per participant. The trials were too small to assess whether or not antifibrinolytics increased the risk of thromboembolic events or other adverse events. There are three ongoing RCTs (1276 participants) due to be completed in 2017 and 2020.
Topics: Aminocaproic Acid; Antifibrinolytic Agents; Erythrocyte Transfusion; Hematologic Diseases; Hemorrhage; Humans; Lysine; Platelet Transfusion; Thrombocytopenia; Thromboembolism; Tranexamic Acid
PubMed: 26978005
DOI: 10.1002/14651858.CD009733.pub3