Journal of Hematology and Oncology via MedWorm.com

Deregulation of apoptosis-related genes is associated with PRV1 overexpression and JAK2 V617F allele burden in Essential Thrombocythemia and Myelofibrosis

Journal of Hematology and Oncology — Thu, 02 Feb 2012 05:00:00 +0100

Conclusions: Our results suggest the participation of intrinsic apoptosis pathway in the MPN physiopathology. In addition, PRV1 and JAK2 V617F allele burden were linked to deregulation of the apoptotic machinery. (Source: Journal of Hematology and Oncology)

Speciation of arsenic trioxide metabolites in peripheral blood and bone marrow from an acute promyelocytic leukemia patient

Journal of Hematology and Oncology — Tue, 24 Jan 2012 05:00:00 +0100

Conclusions: The behaviors of arsenic speciation suggested for the first time that arsenic speciation analysis of PB plasma could be predicative for BM speciation, and showed relatively higher efficiency of drug metabolism in the patient. These results may further provide not only significance of clinical application of ATO, but also a new insight into host defense mechanisms in APL patients undergoing ATO treatment, since HMW proteins-bound arsenic complex could be thought to protect BM from the attack of free arsenic species. (Source: Journal of Hematology and Oncology)

Isolation, characterization, and in vitro propagation of infantile hemangioma stem cells and an in vivo mouse model

Journal of Hematology and Oncology — Thu, 22 Dec 2011 05:00:00 +0100

Conclusions: The ability to propagate large numbers of IH stem cells in vitro and the generation of an in vivo mouse model provides novel avenues for testing IH therapeutic agents in the future. (Source: Journal of Hematology and Oncology)

Methoxyflavone derivatives modulate the effect of TRAIL-induced apoptosis in human leukemic cell lines

Journal of Hematology and Oncology — Wed, 21 Dec 2011 05:00:00 +0100

Conclusion: Methoxyflavone derivatives enhanced TRAIL-induced apoptosis in human leukemic MOLT-4 cells through the death receptors and mitochondrial pathways. (Source: Journal of Hematology and Oncology)

Pharmacological basis and clinical evidence of dabigatran therapy.

Journal of Hematology and Oncology — Wed, 21 Dec 2011 05:00:00 +0100

Dabigatran is an emerging oral anticoagulant which is a direct inhibitor of thrombin activity. It has been approved in the European Union and the United States of America for the prevention of thrombosis after major orthopedic surgery. It has been recently approved by the American Food and Drug Administration and the European Medicines Agency for the prevention of stroke in chronic atrial fibrillation. Dabigatran provides a stable anticoagulation effect without any need to perform periodical laboratory controls. Of note, there is a growing burden of clinical evidence which shows its safety and efficacy. For these reasons, dabigatran may suppose a revolution in oral anticoagulation. However, two important limitations remain. First, it is contraindicated in patients with end-stage renal dise...

Ayurvedic herbal medicine and lead poisoning

Journal of Hematology and Oncology — Tue, 20 Dec 2011 05:00:00 +0100

Although the majority of published cases of lead poisoning come from occupational exposures, some traditional remedies may also contain toxic amounts of lead. Ayurveda is a system of traditional medicine that is native to India and is used in many parts of world as an alternative to standard treatment regimens. Here, we report the case of a 58-year-old woman who presented with abdominal pain, anemia, liver function abnormalities, and an elevated blood lead level. The patient was found to have been taking the Ayurvedic medicine Jambrulin prior to presentation. Chemical analysis of the medication showed high levels of lead. Following treatment with an oral chelating agent, the patient's symptoms resolved and laboratory abnormalities normalized. This case highlights the need for increased awa...

The Four Types of Tregs in Malignant Lymphomas

Journal of Hematology and Oncology — Fri, 09 Dec 2011 05:00:00 +0100

Regulatory T cells (Tregs) are a specialized subpopulation of CD4+ T cells, which act to suppress the activation of other immune cells. Tregs represent important modulators for the interaction between lymphomas and host microenvironment. Lymphomas are a group of serious and frequently fatal malignant diseases of lymphocytes. Recent studies revealed that some lymphoma T cells might adopt a Treg profile. Assessment of Treg phenotypes and genotypes in patients may offer prediction of outcome in many types of lymphomas including diffuse large B-cell lymphoma, follicular lymphoma, cutaneous T cell lymphoma, and Hodgkin's lymphoma. Based on characterized roles of Tregs in lymphomas, we can categorize the various roles into four groups: (a) suppressor Tregs; (b) malignant Tregs; (c) direct tumor-...

The HB22.7 Anti-CD22 Monoclonal Antibody Enhances Bortezomib-mediated Lymphomacidal Activity in a Sequence Dependent Manner

Journal of Hematology and Oncology — Thu, 01 Dec 2011 05:00:00 +0100

Most non-Hodgkin's lymphomas (NHL) initially respond to chemotherapy, but relapse is common and treatment is often limited by chemotherapy-related toxicity. Bortezomib, is a highly selective proteasome inhibitor with anti-NHL activity; it is currently FDA approved for second-line treatment of mantle cell lymphoma (MCL). Bortezomib exerts its activity in part through the generation of reactive oxygen species (ROS) and also by the induction of apoptosis.We previously validated CD22 as a potential target in treating NHL and have shown that the anti-CD22 ligand blocking antibody, HB22.7, has significant independent lymphomacidal properties in NHL xenograft models. We sought to determine whether or not these agents would work synergistically to enhance cytotoxicity. Our results indicate that tr...

T cell receptor transgenic lymphocytes inflitrating murine tumors are not induced to express foxp3

Journal of Hematology and Oncology — Wed, 23 Nov 2011 05:00:00 +0100

Regulatory T cells (Treg) that express the transcription factor Foxp3 are enriched within a broad range of murine and human solid tumors. The ontogeny of these Foxp3 Tregs - selective accumulation or proliferation of natural thymus-derived Treg (nTreg) or induced Treg (iTreg) converted in the periphery from naive T cells - is not known. We used several strains of mice in which Foxp3 and EGFP are coordinately expressed to address this issue. We confirmed that Foxp3-positive CD4 T cells are enriched among tumor-infiltrating lymphocytes (TIL) and splenocytes (SPL) in B16 murine melanoma-bearing C57BL/6 Foxp3EGFP mice. OT-II Foxp3EGFP mice are essentially devoid of nTreg, having transgenic CD4 T cells that recognize a class II-restricted epitope derived from ovalbumin; Foxp3 expression could n...

Light chain (AL) amyloidosis: update on diagnosis and management

Journal of Hematology and Oncology — Fri, 18 Nov 2011 05:00:00 +0100

Light chain (AL) amyloidosis is a plasma cell dyscrasia characterized by the pathologic production of fibrillar proteins comprised of monoclonal light chains which deposit in tissues and cause organ dysfunction. The diagnosis can be challenging, requiring a biopsy and often specialized testing to confirm the subtype of systemic disease. The goal of treatment is eradication of the monoclonal plasma cell population and suppression of the pathologic light chains which can result in organ improvement and extend patient survival. Standard treatment approaches include high dose melphalan (HDM) followed by autologous hematopoietic stem cell transplantation (SCT) or oral melphalan with dexamethasone (MDex). The use of novel agents (thalidomide, lenalidomide and bortezomib) alone and in combinat...

A meta-analysis of CAG (cytarabine, aclarubicin, G-CSF) regimen for the treatment of 1029 patients with acute myeloid leukemia and myelodysplastic syndrome

Journal of Hematology and Oncology — Mon, 14 Nov 2011 05:00:00 +0100

The regimen of cytarabine, aclarubicin and G-CSF (CAG) has been widely used in China and Japan for treatment of acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). We searched literature on CAG between 1995 and 2010 and performed a meta-analysis to determine its overall efficacy using a random-effects or fixed-effects model. Thirty five trials with a total of 1029 AML (n=814) and MDS (n=215) patients were included for analysis. The CR rate of AML (57.9%) was significantly higher than that of MDS (45.7%) (p0.05). The CR rate was also significantly higher in patients with favorable (64.5%) and intermediate (69.6%) karyotypes than those with unfavorable one (29.5%) (p (Source: Journal of Hematology and Oncology)

De novo acute megakaryoblastic leukemia with p210 BCR/ABL and t(1;16) translocation but not t(9;22) Ph chromosome

Journal of Hematology and Oncology — Thu, 10 Nov 2011 05:00:00 +0100

Acute megakaryoblastic leukemia (AMKL) is a type of acute myeloid leukemia (AML), in which majority of the blasts are megakaryoblastic. De novo AMKL in adulthood is rare, and carries very poor prognosis. We here report a 45-year-old woman with de novo AMKL with BCR/ABL rearrangement and der(16)t(1;16)(q21;q23) translocation but negative for t(9;22) Ph chromosome. Upon induction chemotherapy consisting of homoharringtonine, cytarabine and daunorubicin, the patient achieved partial hematological remission. The patient was then switched to imatinib plus one cycle of CAG regimen (low-dose cytarabine and aclarubicin in combination with granulocyte colony-stimulating factor), and achieved complete remission (CR). The disease recurred after 40 days and the patient eventually died of infection. To...

Novel agents for anti-platelet therapy

Journal of Hematology and Oncology — Fri, 04 Nov 2011 04:00:00 +0100

Anti-platelet therapy plays an important role in the treatment of patients with thrombotic diseases. The most commonly used anti-platelet drugs, namely, aspirin, ticlopidine, and clopidogrel, are effective in the prevention and treatment of cardio-cerebrovascular diseases. Glycoprotein IIb/IIIa antagonists (e.g., abciximab, eptifibatide and tirofiban) have demonstrated good clinical benefits and safety profiles in decreasing ischemic events in acute coronary syndrome. However, adverse events related to thrombosis or bleeding have been reported in cases of therapy with glycoprotein IIb/IIIa antagonists. Cilostazol is an anti-platelet agent used in the treatment of patients with peripheral ischemia, such as intermittent claudication. Presently, platelet adenosine diphosphate P2Y(12) receptor...

Oral ezatiostat HCl (Telintra(R), TLK199) and Idiopathic Chronic Neutropenia (ICN): A case report of complete response of a patient with G-CSF resistant ICN following teatment with ezatiostat, a glutathione S-transferase P1-1 (GSTP1-1) inhibitor

Journal of Hematology and Oncology — Wed, 02 Nov 2011 04:00:00 +0100

Idiopathic chronic neutropenia (ICN) describes a heterogeneous group of hematologic diseases characterized by low circulating neutrophil levels often associated with recurrent fevers, chronic mucosal inflammation, and severe systemic infections. The severity and risk of complications, including serious infections, are inversely proportional to the absolute neutrophil count (ANC), with the greatest problems occurring in patients with an ANC of less than 0.5 x 10^9/L. This case report describes a 64-year-old female with longstanding rheumatoid arthritis who subsequently developed ICN with frequent episodes of sepsis requiring hospitalization and prolonged courses of antibiotics over a 4-year period. She was treated with granulocyte colony stimulating factors (G-CSF) but had a delayed, highly...

The impact of therapy for childhood acute lymphoblastic leukaemia on intelligence quotients; results of the risk-stratified randomized central nervous system treatment trial MRC UKALL XI

Journal of Hematology and Oncology — Thu, 13 Oct 2011 04:00:00 +0100

Backgound: The MRC UKALLXI trial tested the efficacy of different central nervous system (CNS) directed therapies in childhood acute lymphoblastic leukaemia (ALL). To evaluate morbidity 555/1826 randomised children underwent prospective psychological evaluations. Full Scale, verbal and performance IQs were measured at 5 months, 3 years and 5 years. Scores were compared in; (1) all patients (n=555) versus related controls (n=311), (2) low-risk children (presenting white cell count (WCC) (Source: Journal of Hematology and Oncology)

Impact of Bile Acids on the Growth of Human Cholangiocarcinoma via FXR

Journal of Hematology and Oncology — Wed, 12 Oct 2011 04:00:00 +0100

Conclusions: The imbalance of ratio of free and conjugated bile acids may play an important role in tumorigenesis of cholangiocarcinoma. FXR, a member of the nuclear receptor superfamily, may mediate the effects induced by the bile acids. (Source: Journal of Hematology and Oncology)

Development of a Highly Sensitive Method for Detection of JAK2V617F

Journal of Hematology and Oncology — Mon, 10 Oct 2011 04:00:00 +0100

Conclusions: We have developed a highly sensitive method that will allow for detection of JAK2V617F at a very early stage. This method may have major implications in diagnosis and prevention of MPNs and related diseases. (Source: Journal of Hematology and Oncology)

Acute myeloid leukemia of donor origin after allogeneic stem cell transplantation from a sibling who harbors germline XPD and XRCC3 homozygous polymorphisms

Journal of Hematology and Oncology — Tue, 27 Sep 2011 04:00:00 +0100

A 54-year-old woman was diagnosed with infiltrative ductal breast carcinoma. Two years after treatment, the patient developed an acute myeloid leukemia (AML) which harbored del(11q23) in 8% of the blast cells. The patient was submitted for allogeneic stem cell transplantation (aSCT) from her HLA-compatible sister. Ten months after transplantation, she relapsed with an AML with basophilic maturation characterized by CD45low CD33high, CD117+, CD13-/+, HLA Drhigh, CD123high, and CD203c+ blast cells lacking expression of CD7, CD10, CD34, CD15, CD14, CD56, CD36, CD64, and cytoplasmic tryptase. Karyotype analysis showed the emergence of a new clone with t(2;14) and FISH analysis indicated the presence of MLL gene rearrangement consistent with del(11q23). Interestingly, AML blast cell DNA tested ...

Enhanced Self-Renewal of Hematopoietic Stem/Progenitor Cells Mediated by the Stem Cell Gene Sall4

Journal of Hematology and Oncology — Fri, 23 Sep 2011 04:00:00 +0100

Conclusion: Sall4 is a potent regulator for HSC/HPC self-renewal, likely by increasing self-renewal activity and inhibiting differentiation. Our work provides further support that Sall4 manipulation may be a new model for expanding clinically transplantable stem cells. (Source: Journal of Hematology and Oncology)

Suppressing miRNA-15a/-16 expression by interleukin-6 enhances drug-resistance in myeloma cells

Journal of Hematology and Oncology — Thu, 22 Sep 2011 04:00:00 +0100

In conclusion, our data suggest that via suppressing miRNA-15a and -16 expression, IL-6 secreted by BMSCs promotes drug-resistance in myeloma cells. (Source: Journal of Hematology and Oncology)

Current findings for recurring mutations in acute myeloid leukemia

Journal of Hematology and Oncology — Wed, 14 Sep 2011 04:00:00 +0100

The development of acute myeloid leukemia (AML) is a multistep process that requires at least two genetic abnormalities for the development of the disease. The identification of genetic mutations in AML has greatly advanced our understanding of leukemogenesis. Recently, the use of novel technologies, such as massively parallel DNA sequencing or high-resolution single-nucleotide polymorphism arrays, has allowed the identification of several novel recurrent gene mutations in AML. The aim of this review is to summarize the current findings for the identification of these gene mutations (Dnmt, TET2, IDH1/2, NPM1, ASXL1, etc.), most of which are frequently found in cytogenetically normal AML. The cooperative interactions of these molecular aberrations and their interactions with class I/II muta...

Chemotherapy in advanced bladder cancer: current status and future

Journal of Hematology and Oncology — Fri, 09 Sep 2011 04:00:00 +0100

Bladder cancer occurs in the majority of cases in males. It represents the seventh most common cancer and the ninth most common cause of cancer deaths for men. Transitional cell carcinoma is the most predominant histological type. Bladder cancer is highly chemosensitive. In metastatic setting, chemotherapy based on cisplatin should be considered as standard treatment of choice for patients with good performance status (0-1) and good renal function-glomerular filtration rate (GFR) > 60 mL/min. The standard treatment is based on cisplatin chemotherapy regimens type MVAC, HD-MVAC, gemcitabine plus cisplatin (GC) or dose dense GC. In unfit patients, carboplatin based regimes; gemcitabine plus carboplatin or methotrexate plus carboplatin plus vinblastine (MCAVI) are reasonable options. The role...

Lymphopenia is an important prognostic factor in peripheral T-cell lymphoma (NOS) treated with anthracycline-containing chemotherapy

Journal of Hematology and Oncology — Sun, 14 Aug 2011 23:00:00 +0100

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Significance of Differential Expression of Thymidylate Synthase in Normal and Primary Tumor Tissues from Patients with Colorectal Cancer

Journal of Hematology and Oncology — Mon, 08 Aug 2011 23:00:00 +0100

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Dasatinib preferentially induces apoptosis by inhibiting Lyn kinase in nilotinib-resistant chronic myeloid leukemia cell line.

Journal of Hematology and Oncology — Mon, 01 Aug 2011 23:00:00 +0100

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High nuclear expression of STAT3 is associated with unfavorable prognosis in diffuse large B-cell lymphoma

Journal of Hematology and Oncology — Sun, 31 Jul 2011 23:00:00 +0100

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Targeting insulin-like growth factor axis in hepatocellular carcinoma

Journal of Hematology and Oncology — Mon, 04 Jul 2011 23:00:00 +0100

The insulin-like growth factor (IGF) axis contains ligands, receptors, substrates, and ligand binding proteins. The essential role of IGF axis in hepatocellular carcinoma (HCC) has been illustrated in HCC cell lines and in animal xenograft models. Preclinical evidence provides ample indication that all four components of IGF axis are crucial in the carcinogenic and metastatic potential of HCC. Several strategies targeting this system including monoclonal antibodies against the IGF 1 receptor (IGF-1R) and small molecule inhibitors of the tyrosine kinase function of IGF-1R are under active investigation. This review describes the most up-to-date understanding of this complex axis in HCC, and provides relevant information on clinical trials targeting the IGF axis in HCC with a focus on anti-I...

Evolving diagnostic and treatment strategies for pancreatic neuroendocrine tumors

Journal of Hematology and Oncology — Mon, 13 Jun 2011 23:00:00 +0100

Pancreatic neuroendocrine tumors (NET) have diverse clinical presentations. Patients with symptoms of hormone secretion may require specific medical interventions to control those symptoms prior to antitumor intervention. In some patients, tumors in the pancreas may be occult and specialized diagnostic imaging or surgery may be required for diagnosis. Other patients have more advanced disease, presenting with symptoms of tumor bulk rather than hormone secretion. Treatment options for patients with advanced pancreatic neuroendocrine tumors include surgical resection and hepatic directed therapies, including partial hepatectomy, hepatic artery embolization, or other ablative techniques. Streptozocin or temozolomide-based chemotherapy regimens are active against pancreatic NET, and can also p...

Clinical observations on intensive immunosuppressive therapy combined with umbilical cord blood support for the treatment of severe aplastic anemia

Journal of Hematology and Oncology — Thu, 09 Jun 2011 23:00:00 +0100

Conclusion: Enhanced, intensive, immuno-suppressive therapy with umbilical cord blood support may be an effective option for SAA therapy. (Source: Journal of Hematology and Oncology)

CyberKnife Stereotactic Radiosurgery for Recurrent, Metastatic, and Residual Hemangiopericytomas

Journal of Hematology and Oncology — Sun, 05 Jun 2011 23:00:00 +0100

Conclusions: : CK is an effective and safe management option for for hemangiopericytomas. The current series demonstrates a tumor control of 81.8%. Other institutions have demonstrated similar outcomes with stereotactic radiosurgery, with tumor control ranging from 46.4% to 100%. (Source: Journal of Hematology and Oncology)

Endothelial progenitor cell biology in disease and tissue regeneration

Journal of Hematology and Oncology — Mon, 23 May 2011 23:00:00 +0100

Endothelial progenitor cells are increasingly being studied in various diseases ranging from ischemia, diabetic retinopathy, and in cancer. The discovery that these cells can be mobilized from their bone marrow niche to sites of inflammation and tumor to induce neovasculogenesis has afforded a novel opportunity to understand the tissue microenvironment and specific cell-cell interactive pathways. This review provides a comprehensive up-to-date understanding of the physiological function and therapeutic utility of these cells. The emphasis is on the systemic factors that modulate their differentiation/mobilization and survival and presents the challenges of its potential therapeutic clinical utility as a diagnostic and prognostic reagent. (Source: Journal of Hematology and Oncology)

Gene expression profiles in BCL11B-siRNA treated malignant T cells

Journal of Hematology and Oncology — Sat, 14 May 2011 23:00:00 +0100

Conclusion: BCL11B-siRNA treatment altered expression profiles of TNFSF10, BCL2L1, and SPP1 in both Molt-4 T cell line and primary T-ALL cells. (Source: Journal of Hematology and Oncology)

Circulating osteopontin: a dual marker of bone destruction and angiogenesis in patients with multiple myeloma.

Journal of Hematology and Oncology — Sat, 07 May 2011 23:00:00 +0100

The matrix protein osteopontin has been shown to be a marker of osteoclastic activity in multiple myeloma patients, as well as a regulator of angiogenesis. We measured serum levels of osteopontin in 50 untreated multiple myeloma patients (in 25, also after treatment) and examined the relation to markers of osteolytic and angiogenic activity. The median (range) of serum osteopontin was 85 (5-232) in the patient group vs. 36 (2-190) ng/ml in the control group. Serum osteopontin levels were significantly higher in patients with advanced stage or grade of myeloma disease. All patients with serum osteopontin levels >100 ng/ml had advanced stage (II or III) or high grade bone disease, whereas stage I or low grade patients had serum osteopontin levels (Source: Journal of Hematology and Oncology)

Expression and distribution of PPP2R5C gene in leukemia

Journal of Hematology and Oncology — Thu, 05 May 2011 23:00:00 +0100

Conclusions: Overexpression of PPP2R5C in T-cell malignancy as well as in myeloid leukemia cells might relate to its proliferation and differentiation. Investigation of the effect of target inhibition of this gene might be beneficial to further characterization of molecular mechanisms and targeted therapy in leukemia. (Source: Journal of Hematology and Oncology)

Retinoic acid induces HL-60 cell differentiation via the upregulation of miR-663

Journal of Hematology and Oncology — Sun, 24 Apr 2011 23:00:00 +0100

Conclusions: Our results show miR-663 may play an important role in ATRA induced HL-60 cell differentiation. Lentivirus delivery of miR-663 could potentially be used directly as an anticancer treatment in hematological malignancies. (Source: Journal of Hematology and Oncology)

Progression of metastatic castrate-resistant prostate cancer: impact of therapeutic intervention in the post-docetaxel space

Journal of Hematology and Oncology — Fri, 22 Apr 2011 23:00:00 +0100

Despite the proven success of hormonal therapy for prostate cancer using chemical or surgical castration, most patients eventually will progress to a phase of the disease that is metastatic and shows resistance to further hormonal manipulation. This has been termed metastatic castrate-resistant prostate cancer (mCRPC). Despite this designation, however, there is evidence that androgen receptor (AR)-mediated signaling and gene expression can persist in mCRPC, even in the face of castrate levels of androgen. This may be due in part to the upregulation of enzymes involved in androgen synthesis, the overexpression of AR, or the emergence of mutant ARs with promiscuous recognition of various steroidal ligands. The therapeutic options were limited and palliative in nature until trials in 2004 de...

Frequency analysis of TRBV subfamily sjTRECs to characterize T-cell reconstitution in acute leukemia patients after allogeneic hematopoietic stem cell transplantation

Journal of Hematology and Oncology — Fri, 22 Apr 2011 23:00:00 +0100

Conclusions: Reconstitution of thymic output function resulted in a period of immunodeficiency, with low or undetectable TRECs after transplantation, although fludarabine-based dose-reduced conditioning regimens were used. GVHD could affect reconstitution of thymic output function and reduce sjTRECs levels and frequencies of TRBV-BD1 sjTRECs. Low frequency of BV22-BD1 and BV23-BD1 sjTRECs might be associated with GVHD. (Source: Journal of Hematology and Oncology)

Novel targeted therapeutics: inhibitors of MDM2, ALK and PARP

Journal of Hematology and Oncology — Tue, 19 Apr 2011 23:00:00 +0100

We have reviewed preclinical data and clinical development of MDM2 (murine double minute 2), ALK (anaplastic lymphoma kinase) and PARP (Poly [ADP-ribose] polymerase) inhibitors. MDM2 binds to p53, and promotes degradation of p53 through ubiquitin-proteasome degradation. JNJ-26854165 and RO5045337 are 2 small-molecule inhibitors of MDM2 in clinical development. ALK is a transmembrane protein and a member of the insulin receptor tyrosine kinases. EML4-ALK fusion gene is identified in approximately 3-13% of non-small cell lung cancer (NSCLC). Early-phase clinical studies with Crizotinib, an ALK inhibitor, in NSCLC harboring EML4-ALK have demonstrated promising activity with high response rate and prolonged progression-free survival. PARPs are a family of nuclear enzymes that regulates the rep...

Histone deacetylases (HDACs) in XPC gene silencing and bladder cancer

Journal of Hematology and Oncology — Tue, 19 Apr 2011 23:00:00 +0100

Bladder cancer is one of the most common malignancies and causes hundreds of thousands of deaths worldwide each year. Bladder cancer is strongly associated with exposure to environmental carcinogens. It is believed that DNA damage generated by environmental carcinogens and their metabolites causes development of bladder cancer. Nucleotide excision repair (NER) is the major DNA repair pathway for repairing bulk DNA damage generated by most environmental carcinogens, and XPC is a DNA damage recognition protein required for initiation of the NER process. Recent studies demonstrate reduced levels of XPC protein in tumors for a majority of bladder cancer patients. In this work we investigated the role of histone deacetylases (HDACs) in XPC gene silencing and bladder cancer development. The resu...

Altered protein expression in serum from endometrial hyperplasia and carcinoma patients

Journal of Hematology and Oncology — Wed, 13 Apr 2011 23:00:00 +0100

Conclusions: The differentially expressed proteins we discovered in this study may serve as biomarkers in the diagnosis and follow-up of endometrial hyperplasia and endometrial carcinoma. (Source: Journal of Hematology and Oncology)

Frequency of intravascular large B-cell lymphoma in Japan: Study of the Osaka Lymphoma Study Group

Journal of Hematology and Oncology — Sun, 10 Apr 2011 23:00:00 +0100

Intravascular large B-cell lymphomaB-IVLis listed as a distinct disease entity in the World Health Organization(WHO) classification for lymphoid neoplasms . The disease is rare, and information for its exact frequency among non-Hodgkin lymphomaNHLhas been extremely limited. There have been several reports mainly from Asian countries describing the different disease frequencies . In addition, population of the cases was variously described among these reports. Therefore it is difficult to know the geographical difference in disease frequency, which might be helpful for understanding pathogenesis of disease.Osaka Lymphoma Study Group (OLSG) was established in 1999, and more than 60 institutes in Osaka area, Japan participate to it. Until present, 5,085 cases of lymphoproliferative diseases h...

Downstream molecular pathways of FLT3 in the pathogenesis of acute myeloid leukemia: biology and therapeutic implications

Journal of Hematology and Oncology — Thu, 31 Mar 2011 23:00:00 +0100

FLT3 is a type III receptor tyrosine kinase. Mutations of FLT3 comprise one of the most frequently identified types of genetic alterations in acute myeloid leukemia. One-third of acute myeloid leukemia patients have mutations of this gene, and the majority of these mutations involve an internal tandem duplication in the juxtamembrane region of FLT3, leading to constitutive activation of downstream signaling pathways and aberrant cell growth. This review summarizes the current understanding of the effects of the downstream molecular signaling pathways after FLT3 activation, with a particular focus on the effects on transcription factors. Moreover, this review describes novel FLT3-targeted therapies, as well as efficient combination therapies for FLT3-mutated leukemia cells. (Source: Journal...

Low incidence of new biochemical and clinical hypogonadism following hypofractionated stereotactic body radiation therapy (SBRT) monotherapy for low- to intermediate-risk prostate cancer

Journal of Hematology and Oncology — Sun, 27 Mar 2011 00:00:00 +0100

Conclusions: Hypofractionated SBRT offers the radiobiological benefit of a large fraction size and is well-tolerated by men with low- to intermediate-risk prostate cancer. Early results are encouraging with an excellent biochemical response. The rate of new biochemical and clinical hypogonadism was low one year after treatment. (Source: Journal of Hematology and Oncology)

A meta-analysis of gemcitabine containing chemotherapy for locally advanced and metastatic pancreatic adenocarcinoma

Journal of Hematology and Oncology — Sat, 26 Mar 2011 00:00:00 +0100

Conclusions: Gemcitabine in combination with capecitabine or oxaliplatin was associated with enhanced OS and ORR as compared with gemcitabine in monotherapy, which are likely to become the preferred standard first-line treatment of LA/MPC. (Source: Journal of Hematology and Oncology)

Mast cell activation disease: A concise practical guide for diagnostic workup and therapeutic options

Journal of Hematology and Oncology — Tue, 22 Mar 2011 00:00:00 +0100

Mast cell activation disease comprises disorders characterized by accumulation of genetically altered mast cells and/or abnormal release of these cells' mediators, affecting functions in potentially every organ system, often without causing abnormalities in routine laboratory or radiologic testing. In most cases of mast cell activation disease, diagnosis is possible by relatively non-invasive investigation. Effective therapy often consists simply of antihistamines and mast cell membrane-stabilising compounds supplemented with medications targeted at specific symptoms and complications. Mast cell activation disease is now appreciated to likely be considerably prevalent and thus should be considered routinely in the differential diagnosis of patients with chronic multisystem polymorbidity or...

Allogeneic hematopoietic stem cell transplantation for acute leukemia with Gilbert's syndrome

Journal of Hematology and Oncology — Wed, 09 Mar 2011 00:00:00 +0100

Acute leukemia with coexisting Gilbert's syndrome treated by allogeneic hematopoietic stem cell transplantation (allo-HSCT) is rarely reported. Here we described a case whose transaminase levels were almost normal, although transient hyperbilirubinemia repeatedly happened during chemotherapy. (Source: Journal of Hematology and Oncology)

Unfolded protein response in Cancer: the Physician's perspective

Journal of Hematology and Oncology — Wed, 23 Feb 2011 00:00:00 +0100

The unfolded protein response (UPR) is a cascade of intracellular stress signaling events in response to an accumulation of unfolded or misfolded proteins in the lumen of the endoplasmic reticulum (ER). Cancer cells are often exposed to hypoxia, nutrient starvation, oxidative stress and other metabolic dysregulation that cause ER stress and activation of the UPR. Depending on the duration and degree of ER stress, the UPR can provide either survival signals by activating adaptive and antiapoptotic pathways, or death signals by inducing cell death programs. Sustained induction or repression of UPR pharmacologically may thus have beneficial and therapeutic effects against cancer. In this review, we discuss the basic mechanisms of UPR and highlight the importance of UPR in cancer biology. We a...

A single-tube allele specific-polymerase chain reaction to detect T315I resistant mutation in chronic myeloid leukemia patients

Journal of Hematology and Oncology — Tue, 08 Feb 2011 00:00:00 +0100

Conclusion: A single-tube AS-PCR is a rapid and sensitive screening method for T315I mutation. Detection of the most resistant leukemic clone in CML patients undergoing TKI therapy should be feasible with this simple and inexpensive method. (Source: Journal of Hematology and Oncology)

BCR-ABL1-independent PI3Kinase activation causing imatinib-resistance

Journal of Hematology and Oncology — Mon, 07 Feb 2011 00:00:00 +0100

Conclusion: We introduce five Philadelphia-chromosome positive cell lines as TKI-resistance models. None of these cell lines carries mutations in the kinase domain of BCR-ABL1 or other molecular aberrations previously indicted in the context of imatinib-resistance. These cell lines are unique as they dephosphorylate ERK1/2 and STAT5 after treatment with imatinib, while PI3K/AKT1/mTOR activity remains unaffected. Inhibition of AKT1 leads to apoptosis in the imatinib-resistant cell lines. In conclusion, Ph+ cell lines show a form of imatinib-resistance attributable to constitutive activation of the PI3K/AKT1 pathway. Mutations in PIK3CA, as observed in cell line KCL-22, or PI3K activating oncogenes may undelie TKI-resistance in these cell lines. (Source: Journal of Hematology and Oncology)

Molecular mechanism of the schedule-dependent synergistic interaction in EGFR-mutant non-small cell lung cancer cell lines treated with paclitaxel and gefitinib

Journal of Hematology and Oncology — Fri, 21 Jan 2011 00:00:00 +0100

Background Chemotherapy combined concurrently with TKIs produced a negative interaction and failed to improve survival when compared with chemotherapy or TKIs alone in the treatment of non-small cell lung cancer (NSCLC). The present study investigated the sequence-dependent interaction between paclitaxel and gefitinib and clarified the underlying mechanism.Methods The effects on cell proliferation, EGFR signaling pathway, and TGFalpha expression were evaluated in a panel of human NSCLC cell lines harboring EGFR mutations with three different combination sequences: sequential treatment with paclitaxel followed by gefitinib (T->G), sequential treatment with gefitinib followed by paclitaxel (G->T), or concomitant treatment (T+G).Results The sequence-dependent anti-proliferative effects differ...

Relevance of JAK2V617F positivity to hematological diseases - survey of samples from a clinical genetics laboratory

Journal of Hematology and Oncology — Fri, 14 Jan 2011 00:00:00 +0100

Conclusions: Our study suggests that JAK2V617F positivity is associated with specific hematological malignancies and is an excellent diagnostic marker for MPNs. The data also indicate that the nested allele-specific PCR method provides clinically relevant information and should be conducted for all cases suspected of having MPNs as well as for other related diseases. (Source: Journal of Hematology and Oncology)

Two dose-level confirmatory study of the pharmacokinetics and tolerability of everolimus in Chinese patients with advanced solid tumors

Journal of Hematology and Oncology — Thu, 13 Jan 2011 00:00:00 +0100

Conclusions: Everolimus 5 or 10 mg/day was well tolerated in Chinese patients with advanced solid tumors. The observed safety and pharmacokinetic profile of everolimus from this study were consistent with previous studies.Trial registration: Chinese Health Authorities 2008L09346 (Source: Journal of Hematology and Oncology)

Generation of diffuse large B cell lymphoma-associated antigen-specific Valpha6/Vbeta13+T cells by TCR gene transfer

Journal of Hematology and Oncology — Tue, 11 Jan 2011 00:00:00 +0100

Conclusions: Specific anti-DLBCL cytotoxic T lymphocyte (CTL) could be inducted by transduction of specific TCR gene to modify healthy T cells. (Source: Journal of Hematology and Oncology)

Differential Expression of MicroRNAs in CD34+ Cells of 5q- Syndrome

Journal of Hematology and Oncology — Thu, 06 Jan 2011 00:00:00 +0100

Conclusions: The study demonstrates global overexpression of miRNAs is associated with 5q- phenotype. Identification of hematopoiesis-relevant target genes indicates that the deregulated miRNAs may be involved in the pathogenesis of 5q- syndrome by a modulation of these targets. The expression data on miRNAs at del(5q) suggest the presence of mechanisms for compensation of a gene dosage. (Source: Journal of Hematology and Oncology)

HLA-matched sibling transplantation with G-CSF mobilized PBSCs and BM decreases GVHD in adult patients with severe aplastic anemia

Journal of Hematology and Oncology — Fri, 31 Dec 2010 00:00:00 +0100

Conclusion. HSCT with both G-CSF mobilized PB and BMSCs is a promising approach for heavily transfused and/or allo-immunized patients with SAA. (Source: Journal of Hematology and Oncology)

Mitochondrial and endoplasmic reticulum stress pathways cooperate in zearalenone-induced apoptosis of human leukemic cells

Journal of Hematology and Oncology — Thu, 30 Dec 2010 00:00:00 +0100

Conclusion: ZEA induced human leukemic cell apoptosis via endoplasmic stress and mitochondrial pathway. (Source: Journal of Hematology and Oncology)

Therapeutic activity of two xanthones in a xenograft murine model of human chronic lymphocytic leukemia

Journal of Hematology and Oncology — Tue, 07 Dec 2010 00:00:00 +0100

Conclusion: These data show for the first time the in vivo antileukemic activities of two plant-derived xanthones, and confirm their potential interest for CLL therapy. (Source: Journal of Hematology and Oncology)

Therapeutic activity of two xanthones in a xenograft murine model of human chronic lympocytic leukemia

Journal of Hematology and Oncology — Tue, 07 Dec 2010 00:00:00 +0100

Reactivating aberrantly hypermethylated p15 gene in leukemic T cells by a phenylhexyl isothiocyanate mediated inter-active mechanism on DNA and chromatin

Journal of Hematology and Oncology — Mon, 29 Nov 2010 00:00:00 +0100

Background: We have previously demonstrated that phenylhexyl isothiocyanate (PHI), a synthetic isothiocyanate, inhibits histone deacetylases and remodels chromatins to induce growth arrest in HL-60 myeloid leukemia cells in a concentration-dependent manner. Methods: To investigate the effect of PHI, a novel histone deacetylases inhibitor (HDACi), on demethylation and activation of transcription of p15 in acute lymphoid leukemia cell line Molt-4, and to further decipher the potential mechanism of demethylation, DNA sequencing and modified methylation specific PCR (MSP) were used to screen p15-M and p15-U mRNA after Molt-4 cells were treated with PHI, 5-Aza and TSA. DNA methyltransferase 1 (DNMT1), 3A (DNMT3A), 3B (DNMT3B) and p15 mRNA were measured by RT-PCR. P15 protein, acetylated histone...

First-line treatment for chronic myeloid leukemia: dasatinib, nilotinib, or imatinib

Journal of Hematology and Oncology — Fri, 26 Nov 2010 00:00:00 +0100

Imatinib, a tyrosine kinase inhibitor (TKI) of BCR-ABL, was the standard first-line therapy for chronic myeloid leukemia (CML) for almost 10 years. Dasatinib and nilotinib, two newer drugs with higher potency than imatinib against BCR-ABL and activity against most imatinib-resistant BCR-ABL mutations, have each shown superior efficacy compared with imatinib for first-line treatment of chronic-phase CML in randomized phase 3 trials. With 14 months follow-up time, available data suggest no obvious differences in efficacy between dasatinib and nilotinib. Compared with imatinib, dasatinib is associated with higher rates of pleural effusion and thrombocytopenia, but lower rates of edema, gastrointestinal AEs, musculoskeletal AEs, and rash. Nilotinib is associated with higher rates of dermatolog...

Dysregulation of miR-15a and miR-214 in human pancreatic cancer

Journal of Hematology and Oncology — Wed, 24 Nov 2010 00:00:00 +0100

Conclusions: Aberrant expression of miRNAs such as miR-15a and miR-214 results in different cellular effects in pancreatic cancer. Downregulation of miR-15a might contribute to proliferation of pancreatic cancer cells, whereas upregulation of miR-214 in pancreatic cancer specimens might be related to the poor response of pancreatic cancer cells to chemotherapy. MiR-15a directly targets multiple genes relevant in pancreatic cancer, suggesting that it may serve as a novel therapeutic target for treatment of the disease. (Source: Journal of Hematology and Oncology)

Targeted therapy in lymphoma

Journal of Hematology and Oncology — Tue, 23 Nov 2010 00:00:00 +0100

Discovery of new treatments for lymphoma that prolong survival and are less toxic than currently available agents represents an urgent unmet need. We now have a better understanding of the molecular pathogenesis of lymphoma, such as aberrant signal transduction pathways, which have led to the discovery and development of targeted therapeutics. The ubiquitin-proteasome and the Akt/mammalian target of rapamycin (mTOR) pathways are examples of pathological mechanisms that are being targeted in drug development efforts. Bortezomib (a small molecule protease inhibitor) and the mTOR inhibitors temsirolimus, everolimus, and ridaforolimus are some of the targeted therapies currently being studied in the treatment of aggressive, relapsed/refractory lymphoma. This review will discuss the rationale f...

Analysis of the expression pattern of the BCL11B gene and its relatives in patients with T-cell acute lymphoblastic leukemia

Journal of Hematology and Oncology — Tue, 16 Nov 2010 00:00:00 +0100

Conclusions: Over-expression of BCL11B might play a role in anti-apoptosis in T-ALL cells through up-regulation of its downstream genes BCL2L1 and CREBBP. (Source: Journal of Hematology and Oncology)

Lobaplatin arrests cell cycle progression in human hepatocellular carcinoma cells

Journal of Hematology and Oncology — Sun, 31 Oct 2010 00:00:00 +0100

Conclusion: Cytotoxicity of lobaplatin in human HCC cells might be due to its ability to arrest cell cycle progression which would contribute to the potential use of lobaplatin for the management of HCC. (Source: Journal of Hematology and Oncology)

The frequency of NPM1 mutations in childhood acute myeloid leukemia

Journal of Hematology and Oncology — Tue, 26 Oct 2010 23:00:00 +0100

Conclusions: A relatively consistent NPM1 mutation rate was observed, but with variations in types of mutations. The role of different types of NPM1 mutations, either individually or in the presence of other common gene mutations may be essential for childhood AML prognosis. (Source: Journal of Hematology and Oncology)

Treatment Options for Patients with Triple-Negative Breast Cancer

Journal of Hematology and Oncology — Tue, 26 Oct 2010 23:00:00 +0100

Breast cancer is a heterogeneous disease composed of different subtypes, characterized by their different clinicopathological characteristics, prognoses and responses to treatment. In the past decade, significant advances have been made in the treatment of breast cancer sensitive to hormonal treatments, as well as in patients whose malignant cells overexpress or amplify HER2. In contrast, mainly due to the lack of molecular targets, little progress has been made in the treatment of patients with triple-negative breast cancer. Recent improved understanding of the natural history, pathophysiology, and molecular features of triple-negative breast cancers have provided new insights into management and therapeutic strategies for women affected with this entity. Ongoing and planned translational...

The anti-myeloma activity of a novel purine scaffold HSP90 inhibitor PU-H71 is via inhibition of both HSP90A and HSP90B1

Journal of Hematology and Oncology — Mon, 25 Oct 2010 23:00:00 +0100

Conclusion: We conclude that PU-H71 is a promising drug for the treatment of myeloma. Our finding further suggests that PU-H71 and the geldanamycin analogues work in part by inhibiting the endoplasmic reticulum gp96 along with the cytosolic HSP90. (Source: Journal of Hematology and Oncology)

CyberKnife for hilar lung tumors: report of clinical response and toxicity

Journal of Hematology and Oncology — Thu, 21 Oct 2010 23:00:00 +0100

Conclusion: CyberKnife radiosurgery is an effective palliative treatment option for hilar lung tumors, but local control is poor at one year. Maximum point doses to critical structures may be used as a guide for limiting toxicities. Preliminary results suggest that dose escalation alone is unlikely to enhance the therapeutic ratio of hilar lung tumors and novel approaches, such as further defining the patient population or employing the use of radiation sensitizers, should be investigated. (Source: Journal of Hematology and Oncology)

Epigenetic modifications as key regulators of Waldenstrom's Macroglobulinemia biology

Journal of Hematology and Oncology — Wed, 06 Oct 2010 23:00:00 +0100

Waldenstrom's Macroglobulinemia is a low-grade B-cell lymphoma characterized by the presence of lymphoplasmacytic cells in the bone marrow and a monoclonal immunoglobulin M in the circulation. Recent evidences support the hypothesis that epigenetic modifications lead to Waldesntrom cell proliferation and therefore play a crucial role in the pathogenesis of this disease. Indeed, while cytogenetic and gene expression analysis have demonstrated minimal changes; microRNA aberrations and modification in the histone acetylation status of primary Waldenstrom Macroglobulinemia tumor cells have been described. These findings provide a better understanding of the underlying molecular changes that lead to the initiation and progression of this disease. (Source: Journal of Hematology and Oncology)

Pharmacokinetic targeting of intravenous busulfan reduces conditioning regimen related toxicity following allogeneic hematopoietic cell transplantation for acute myelogenous leukemia

Journal of Hematology and Oncology — Tue, 05 Oct 2010 23:00:00 +0100

Optimal conditioning therapy for hematopoietic cell transplantation (HCT) in acute myelogenous leukemia (AML) remains undefined. We retrospectively compared outcomes of a consecutive series of 51 AML patients treated with oral busulfan (1mg/kg every 6 hours for 4 days) and cyclophosphamide (60mg/kg IV x 2 days) - (Bu/Cy) with 100 consecutive AML patients treated with pharmacokinetic targeted IV busulfan (AUC < 6000uM/L*min per day x 4 days) and fludarabine (40mg/m2 x 4 days) - (t-IV Bu/Flu). The Bu/Cy and t-IV Bu/Flu groups significantly differed according to donor relation, stem cell source, aGVHD prophylaxis, remission status, primary vs. secondary disease, median age, and % blasts prior to HCT (p < 0.01 for each). Conditioning with t-IV Bu/Flu reduced early toxicity including idiopathic...

The Clinical Potential of MicroRNAs

Journal of Hematology and Oncology — Tue, 05 Oct 2010 23:00:00 +0100

MicroRNAs (miRNAs) are small noncoding RNAs that function to control gene expression. These small RNAs have been shown to contribute to the control of cell growth, differentiation and apoptosis, important features related to cancer development and progression. In fact, recent studies have shown the utility of miRNAs as cancer-related biomarkers. This is due to the finding that miRNAs display altered expression profiles in cancers versus normal tissue. In addition, miRNAs have been associated with cancer progression. In this review, the mechanisms to alter miRNA expression and their relation to cancer will be addressed. Moreover, the potential application of miRNAs in clinical settings will also be highlighted. Finally, the challenges regarding the translation of research involving miRNAs t...

Autoimmune conditions and hairy cell leukemia: an exploratory case-control study

Journal of Hematology and Oncology — Sun, 03 Oct 2010 23:00:00 +0100

Background: Case reports suggest that hairy cell leukemia (HCL) may be associated with autoimmune conditions, however no systematic investigations in this area have been undertaken. Methods: Using the United States Surveillance, Epidemiology, and End Results Medicare linked database, we conducted an exploratory study comparing autoimmune conditions in 418 HCL cases (aged [greater than or equal to]65 years) and 160,086 controls. Results: Overall, the proportion with autoimmune conditions was similar between HCL cases and controls (n=79 (18.9%) and n=29,284 (18.3%), respectively). Before diagnosis/selection, there was no overall difference in the prevalence of autoimmune conditions in HCL cases (n=37, 8.9%) compared with controls (n=14,085, 8.8%), p=0.969. However, compared with controls, HC...

Acute dyspnoea and single tracheal localisation of mantle cell lymphoma

Journal of Hematology and Oncology — Mon, 27 Sep 2010 23:00:00 +0100

Conclusion: This case illustrates the necessity to ensure the diagnosis of mucosal lymphoma versus MCL since these diseases need different treatment regimens and prognoses. (Source: Journal of Hematology and Oncology)

Role of Wnt canonical pathway in hematological malignancies

Journal of Hematology and Oncology — Tue, 14 Sep 2010 23:00:00 +0100

Wnt canonical signaling pathway plays a diverse role in embryonic development and maintenance of organs and tissues in adults. It has been observed that Wnt/beta-catenin signaling pathway is involved in the pathogenesis of many carcinomas. Moreover, Wnt/beta-catenin pathway has been revealed to be associated with angiogenesis. Wnt canonical pathway signaling has great potential as a therapeutic target. It has been disclosed that some hematological malignancies, such as chronic lymphocytic leukemia, mantle cell lymphoma, may occur partly due to the constitutive activation of Wnt canonical signaling pathway. This review will summarize the latest development in Wnt canonical signaling pathway and its roles in tumorigenesis and angiogenesis. (Source: Journal of Hematology and Oncology)

Prozone effect of serum IgE levels in a case of plasma cell leukemia

Journal of Hematology and Oncology — Thu, 09 Sep 2010 23:00:00 +0100

We describe a case of multiple myeloma (MM) and secondary plasma cell leukemia (PCL) secreting IgE-kappa immunoglobulin. To our knowledge, only 2 cases of IgE-producing secondary PCL have been reported in the medical literature. In our patient, the only tumor marker available for monitoring the therapeutic response to chemotherapy and allogeneic stem cell transplantation was the quantitative M component at serum protein electrophoresis (SPEP), because serum free light chains were in the normal range, Bence-Jones proteinuria was absent, and quantitative serum IgE levels provided inaccurate and erratic results, due to the prozone effect. This is a laboratory phenomenon that occurs when antigen excess interferes with antibody-based methods requiring immune complex formation for detection. It ...

Cytostatic and anti-angiogenic effects of temsirolimus in refractory mantle cell lymphoma

Journal of Hematology and Oncology — Wed, 08 Sep 2010 23:00:00 +0100

Mantle cell lymphoma (MCL) is a rare and aggressive type of B-cell non-Hodgkin's lymphoma. Patients become progressively refractory to conventional chemotherapy, and their prognosis is poor. However, a 38% remission rate has been recently reported in refractory MCL treated with temsirolimus, a mTOR inhibitor.Here we had the opportunity to study a case of refractory MCL who had tumor regression two months after temsirolimus treatment, and a progression-free survival of 10 months. In this case, lymph node biopsies were performed before and six months after temsirolimus therapy. Comparison of the two biopsies showed that temsirolimus inhibited tumor cell proliferation through cell cycle arrest, but did not induce any change in the number of apoptotic tumor cells. Apart from this cytostatic ef...

Pathological complete response after neoadjuvant chemotherapy with trastuzumab-containing regimen in gastric cancer: a case report

Journal of Hematology and Oncology — Wed, 08 Sep 2010 23:00:00 +0100

We report a 49-year-old Chinese male with locally advanced gastric adenocarcinoma achieving pathological complete response after neoadjuvant chemotherapy with trastuzumab-containing regimen. He underwent esophagogastroduodenoscopy in September 2009, which revealed a 2-cm gastric ulcer on the lesser curvature proximal to angularis. Biopsy of gastric ulcer showed moderately differentiated adenocarcinoma with overexpression of human epidermal growth factor receptor 2 (HER2) by immunohistochemistry and fluorescence in situ hybridization. Further workups with endoscopic ultrasound, computed tomography and positron emission tomography staged his cancer as T3N1M0. He received 3 cycles of neoadjuvant chemotherapy consisting of trastuzumab, oxaliplatin, docetaxel and capecitabine without severe tox...

Analysis of Ggamma-158(C->T) polymorphism in hemoglobin E/beta-thalassemia major in Southern China

Journal of Hematology and Oncology — Mon, 06 Sep 2010 23:00:00 +0100

Conclusions: The frequency of the Ggamma-158(C->T) polymorphism was relatively high in southern Chinese patients with HbE/beta-thalassemia major, often accompanying high production of HbF. This feature appears to be different with reports in other races and regions. (Source: Journal of Hematology and Oncology)

Basic Mechanisms of Arsenic Trioxide (ATO)-Induced Apoptosis in Human Leukemia (HL-60) Cells

Journal of Hematology and Oncology — Wed, 25 Aug 2010 23:00:00 +0100

Background: Acute promyelocytic leukemia (APL) is a blood cancer that affects people of all ages and strikes about 1,500 patients in the United States each year. The standard treatment of APL has been based on the combined administration of all-trans retinoic acid and chemotherapy including anthracyclins and cytarabine. However, 10-20% of patients relapse, with their disease becoming resistant to conventional treatment. Recently the Food and Drug Administration has approved the use of arsenic trioxide (ATO) or Trisenox for the treatment of APL, based on clinical studies showing a complete remission, especially in relapsed patients. In a recently published study we demonstrated that ATO pharmacology as an anti-cancer drug is associated with its cytotoxic and genotoxic effects in human leuke...

Hodgkin lymphoma treatment with ABVD in the US and the EU: neutropenia occurrence and impaired chemotherapy delivery

Journal of Hematology and Oncology — Wed, 18 Aug 2010 23:00:00 +0100

Conclusions: In this population of HL patients, CIN and FN occurrence was substantial, and chemotherapy delivery was suboptimal. CSF prophylaxis appeared to reduce CIN rates. (Source: Journal of Hematology and Oncology)

Angiogenesis inhibitors in the treatment of prostate cancer

Journal of Hematology and Oncology — Sun, 01 Aug 2010 23:00:00 +0100

Prostate cancer remains a significant public health problem, with limited therapeutic options in the setting of castrate-resistant metastatic disease. Angiogenesis inhibition is a relatively novel antineoplastic approach, which targets the reliance of tumor growth on the formation of new blood vessels. This strategy has been used successfully in other solid tumor types, with the FDA approval of anti-angiogenic agents in breast, lung, colon, brain, and kidney cancer. The application of anti-angiogenic therapy to prostate cancer is reviewed in this article, with attention to efficacy and toxicity results from several classes of anti-angiogenic agents. Ultimately, the fate of anti-angiogenic agents in prostate cancer rests on the eagerly anticipated results of several key phase III studies. (...

Ring chromosome 18 abnormality in acute myelogenous leukemia: the clinical dilemma

Journal of Hematology and Oncology — Wed, 21 Jul 2010 23:00:00 +0100

The ring chromosome is a circular, structural abnormality composed of either multiple chromosomes or a single chromosome with loss of genetic material at one or both ends. This chromosomal rearrangement is often unstable with frequent recombinations and may be accompanied by either loss or amplification of genetic material.1 Considering that ring chromosomes are rare in acute myelogenous leukemia (AML), it is difficult to risk stratify patient prognosis, particularly when the ring chromosome occurs as the sole abnormality. Here we report a case of a ring chromosome 18 abnormality in a patient with newly diagnosed AML with monocytic differentiation. Cytogenetic analysis demonstrated 46,XY,r(18)(p11q21) karyotype in 19 of 34 evaluated metaphase cells. The patient received induction chemother...

Pancytopenia associated with clonazepam

Journal of Hematology and Oncology — Tue, 13 Jul 2010 23:00:00 +0100

We report a case of a 48-year-old Chinese female with end-stage renal disease and chronic anemia on hemodialysis. Clonazepam was prescribed for myoclonus disorder two weeks prior to her hospitalization. Subsequently, she was hospitalized for neutropenic fever with thrombocytopenia and worsening anemia. Bone marrow examination demonstrated a markedly hypocellular marrow (10-20% total cellularity). Clonazepam was discontinued, with gradual improvement of thrombocytopenia and neutropenia in 1-2 weeks. To our knowledge, this is the first reported case of pancytopenia associated with clonazepam. We recommend patients taking clonazepam to be monitored with regular complete blood count to check for clinically significant pancytopenia or thrombocytopenia. (Source: Journal of Hematology and Oncolog...

Management of stage one and two-E gastric large B-cell lymphoma: chemotherapy alone or surgery followed by chemotherapy?

Journal of Hematology and Oncology — Mon, 21 Jun 2010 23:00:00 +0100

Conclusion: Our data suggest that chemotherapy alone may be a reasonable alternative treatment for stage I/II gastric large-cell lymphoma but this result must be confirmed by prospective randomized clinical trials. (Source: Journal of Hematology and Oncology)

CyberKnife enhanced conventionally fractionated chemoradiation for high grade glioma in close proximity to critical structures

Journal of Hematology and Oncology — Tue, 08 Jun 2010 23:00:00 +0100

Conclusion: We utilized fractionated CyberKnife radiotherapy as an adjunct to conventional radiation to improve the targeting accuracy of high-grade glioma radiation treatment. This technique was safe, effective and allowed for optimal dose-delivery in our patients. The value of image-guided radiation therapy for the treatment of high-grade gliomas deserves further study. (Source: Journal of Hematology and Oncology)

An epidemiological investigation of leukemia incidence between 2003 and 2007 in Nanjing, China

Journal of Hematology and Oncology — Tue, 01 Jun 2010 23:00:00 +0100

Conclusions: The incidence rate of leukemia, especially in the aged population, was relatively high in Nanjing. Leukemia is the major malignant tumor in children. Therefore, more attention should be paid to leukemia in children and the aged people. (Source: Journal of Hematology and Oncology)

Sweet fruit from a poisonous kiss

Journal of Hematology and Oncology — Thu, 27 May 2010 23:00:00 +0100

Acute promyelocytic leukemia (APL), once a rapidly fatal disease, has become most curable of all leukemias, thanks to the two Chinese wonder drugs, all-trans retinoid acid and arsenic trioxide (AT). PML-RAR fusion protein is the hallmark and driving force of APL. In the April 9th issue of the journal, Science, Zhang et al. provided new and convincing evidence on how AT, an ancient poisonous medicine, plays the tricks on the oncoprotein, PML- RAR , and sheds lights on how a poisonous kiss leads to the sweet fruit (Source: Journal of Hematology and Oncology)

Updates in non-small cell lung cancer - insights from the 2009 45th annual meeting of the American Society of Clinical Oncology

Journal of Hematology and Oncology — Sat, 01 May 2010 23:00:00 +0100

We have reviewed the pivotal presentations in non-small cell lung cancer (NSCLC) from the 2009 annual meeting of the American Society of Clinical Oncology. We have discussed the scientific data, the impact on standards of care, and ongoing clinical trials.In patients with early-stage NSCLC, there is still no data to support the superiority of either neoadjuvant or adjuvant chemotherapy. However, adjuvant cisplatin-based chemotherapy has sustained the survival benefits after median follow-up of more than 9 years. The first-line treatment with epidermal growth factor inhibitors could be considered for the treatment of EGFR mutated patients with metastatic disease.Several maintenance studies with cytotoxic or biological agents have also demonstrated promising outcomes. Finally, novel targeted...

Novel agents and regimens for acute myeloid leukemia: 2009 ASH annual meeting highlights

Journal of Hematology and Oncology — Thu, 22 Apr 2010 23:00:00 +0100

Prognostic markers, such as NPM1, Flt3-ITD, and cytogenetic abnormalities have made it possible to formulate aggressive treatment plans for unfavorable acute myeloid leukemia (AML). However, the long-term survival of AML with unfavorable factors remains unsatisfactory. The latest data indicate that the standard dose of daunorubicin (DNR) at 45mg/m2 is inferior to high dose 90 mg/m2 for induction therapy. The rates of complete remission and overall survival are significantly better in the high dose induction regimen. New regimens exploring the new liposomal encapsulation of Ara-C and DNR as well as addition of gemtuzumab ozogamicin monoclonal antibody have been studied. New agents, including the nucleoside analogues (clofarabine, sapacitabine, elacytarabine), FLT3 inhibitor (sorafenib), far...

Oral Ezatiostat HCl (TLK199) and Myelodysplastic syndrome: A case report of sustained hematologic response following an abbreviated exposure

Journal of Hematology and Oncology — Thu, 22 Apr 2010 23:00:00 +0100

Treatment options for patients with lower risk non-del(5q) myelodysplastic syndromes (MDS) who fail erythroid stimulating agents are restricted to one of the hypomethylating drugs with an expected response rate of ~50%. Ezatiostat HCl, an agent with the potential for producing multi-lineage responses in this population is currently in clinical investigation phase. This case report describes a 77 year old male who received less than two cycles of therapy with ezatiostat HCl which had to be aborted due to intolerable side effects, but which produced a sustained normalization of all three blood counts. This trilineage response has now lasted for more than a year. Interestingly, the patient began with a del(5q) abnormality and responded briefly to lenalidomide. Upon relapse of the anemia, a bo...

CD7 in acute myeloid leukemia: correlation with loss of wild-type CEBPA, consequence of epigenetic regulation

Journal of Hematology and Oncology — Tue, 13 Apr 2010 23:00:00 +0100

Conclusion: We confirmed an inverse correlation between the expression of wild-type CEBPA and of CD7 in AML cells. Our results contradict the hypothesis that C/EBPalpha acts as repressor for CD7, and instead show that epigenetic mechanisms are responsible for CD7 regulation, in AML cells as well as in T-cells, the typical CD7 expressing cell type. (Source: Journal of Hematology and Oncology)

Evolution of T-cell clonality in a patient with Ph-negative acute lymphocytic leukemia occurring after interferon and imatinib therapy for Ph-positive chronic myeloid leukemia

Journal of Hematology and Oncology — Thu, 08 Apr 2010 23:00:00 +0100

Conclusions: Restrictive usage and clonal proliferation of different Valpha/Vbeta subfamily T cells between the stages of Ph-positive CP and Ph-negative ALL were detected in one patient. These changes may play a role in Ph- negative leukemogenesis. (Source: Journal of Hematology and Oncology)

Applying mass spectrometry based proteomic technology to advance the understanding of multiple myeloma

Journal of Hematology and Oncology — Tue, 06 Apr 2010 23:00:00 +0100

Multiple myeloma (MM) is the second most common hematological malignancy in adults. It is characterized by clonal proliferation of terminally differentiated B lymphocytes and over-production of monoclonal immunoglobulins. Recurrent genomic aberrations have been identified to contribute to the aggressiveness of this cancer. Despite a wealth of knowledge describing the molecular biology of MM as well as significant advances in therapeutics, this disease remains fatal. The identification of biomarkers, especially through the use of mass spectrometry, however, holds great promise to increasing our understanding of this disease. In particular, novel biomarkers will help in the diagnosis, prognosis and therapeutic stratification of MM. To date, results from mass spectrometry studies of MM have p...

Hypersensitivity reaction and acute immune-mediated thrombocytopenia from oxaliplatin: two case reports and a review of the literature

Journal of Hematology and Oncology — Fri, 26 Mar 2010 00:00:00 +0100

Conclusions: We recommend vigilant monitoring of complete blood count and signs and symptoms of bleeding after the occurrence of oxaliplatin-induced hypersensitivity to avoid the serious complications of immune-mediated thrombocytopenia. (Source: Journal of Hematology and Oncology)

Recent advances in gastrointestinal oncology - updates and insights from the 2009 annual meeting of the American Society of Clinical Oncology

Journal of Hematology and Oncology — Tue, 23 Mar 2010 00:00:00 +0100

We have reviewed the pivotal presentations related to gastrointestinal malignancies from 2009 annual meeting of the American Society of Clinical Oncology with the theme of "personalizing cancer care". We have discussed the scientific findings and the impact on practice guidelines and ongoing clinical trials. Adding trastuzumab to chemotherapy improved the survival of patients with advanced gastric cancer overexpressing human epidermal growth factor receptor 2. Gemcitabine plus cisplatin has become a new standard for first-line treatment of advanced biliary cancer. Octreotide LAR significantly lengthened median time to tumor progression compared with placebo in patients with metastatic neuroendocrine tumors of the midgut. Addition of oxaliplatin to fluoropyrimidines for preoperative chemora...

RRM1 single nucleotide polymorphism -37C->A correlates with progression-free survival in NSCLC patients after gemcitabine-based chemotherapy

Journal of Hematology and Oncology — Sat, 13 Mar 2010 00:00:00 +0100

Conclusions: The RRM1 polymorphism 37C->A correlated with PFS in NSCLC patients treated with gemcitabine-based chemotherapy. No significant correlation was found between PBMC RRM1 mRNA expression and the efficacy of gemcitabine. (Source: Journal of Hematology and Oncology)

Phase 2 study of canfosfamide in combination with pegylated liposomal doxorubicin in platinum and paclitaxel refractory or resistant epithelial ovarian cancer

Journal of Hematology and Oncology — Thu, 11 Mar 2010 00:00:00 +0100

Conclusions: Canfosfamide in combination with PLD is well tolerated and active in platinum and paclitaxel refractory or resistant ovarian cancer. A randomized phase 3 study was conducted based on this supportive phase 2 study.Trial Registration: This study was registered at www.clinicaltrials.gov: NCT00052065. (Source: Journal of Hematology and Oncology)

From basic research to clinical development of MEK1/2 inhibitors for cancer therapy

Journal of Hematology and Oncology — Thu, 11 Feb 2010 00:00:00 +0100

The Ras-dependent Raf/MEK/ERK1/2 mitogen-activated protein (MAP) kinase signaling pathway is a major regulator of cell proliferation and survival. Not surprisingly, hyperactivation of this pathway is frequently observed in human malignancies as a result of aberrant activation of receptor tyrosine kinases or gain-of-function mutations in RAS or RAF genes. Components of the ERK1/2 pathway are therefore viewed as attractive candidates for the development of targeted therapies of cancer. In this article, we briefly review the basic research that has laid the groundwork for the clinical development of small molecules inhibitors of the ERK1/2 pathway. We then present the current state of clinical evaluation of MEK1/2 inhibitors in cancer and discuss challenges ahead. (Source: Journal of Hematolo...

Ovarian cancer immunotherapy: opportunities, progresses and challenges

Journal of Hematology and Oncology — Wed, 10 Feb 2010 00:00:00 +0100

Due to the low survival rates from invasive ovarian cancer, new effective treatment modalities are urgently needed. Compelling evidence indicates that the immune response against ovarian cancer may play an important role in controlling this disease. We herein summarize multiple immune-based strategies that have been proposed and tested for potential therapeutic benefit against advanced stage ovarian cancer. We will examine the evidence for the premise that an effective therapeutic vaccine against ovarian cancer is useful not only for inducing remission of the disease but also for preventing disease relapse. We will also highlight the questions and challenges in the development of ovarian cancer vaccines, and critically discuss the limitations of some of the existing immunotherapeutic strat...

CyberKnife radiosurgery for inoperable stage IA non-small cell lung cancer: 18F-fluorodeoxyglucose positron emission tomography/computed tomography serial tumor response assessment

Journal of Hematology and Oncology — Thu, 04 Feb 2010 00:00:00 +0100

Conclusion: Local control and survival following CyberKnife radiosurgery for stage IA NSCLC is exceptional. Early transient increases in tumor SUVmax are likely related to radiation-induced pneumonitis. Tumor SUVmax values return to background levels at 18-24 months, enhancing 18F-FDG PET/CT detection of local failure. The value of18F-FDG PET/CT imaging for surveillance following lung SBRT deserves further study. (Source: Journal of Hematology and Oncology)

Novel histone deacetylase inhibitors in clinical trials as anti-cancer agents

Journal of Hematology and Oncology — Thu, 04 Feb 2010 00:00:00 +0100

Histone deacetylases (HDACs) can regulate expression of tumor suppressor genes and activities of transcriptional factors involved in both cancer initiation and progression through alteration of either DNA or the structural components of chromatin. Recently, the role of gene repression through modulation such as acetylation in cancer patients has been clinically validated with several inhibitors of HDACs. One of the HDAC inhibitors, vorinostat, has been approved by FDA for treating cutaneous T-cell lymphoma (CTCL) for patients with progressive, persistent, or recurrent disease on or following two systemic therapies. Other inhibitors, for example, FK228, PXD101, PCI-24781, ITF2357, MGCD0103, MS-275, valproic acid and LBH589 have also demonstrated therapeutic potential as monotherapy or combi...

Complete response to FOLFOX4 therapy in a patient with advanced urothelial cancer: a case report

Journal of Hematology and Oncology — Wed, 20 Jan 2010 00:00:00 +0100

We report the complete response to FOLFOX4 therapy of a metastatic urothelial cancer patient, for whom adjuvant gemcitabine plus cisplatin combination chemotherapy had failed. A 54-year-old male patient with urothelial cancer (transitional cell carcinoma) in the right kidney underwent three rounds of adjuvant gemcitabine-cisplatin chemotherapy after extensive radical nephrectomy. However, he had new liver, lung metastases and synchronous two separate primary colon cancer. The lung metastasis lesion was confirmed as a metastatic urothelial cancer via percutaneous transthoracic needle biopsy (PTNB). Liver and lung metastasis lesions disappeared after the 4th cycle of FOLFOX4 chemotherapy. In addition, colon cancer also disappeared after the 8th cycle of FOLFOX4 chemotherapy. The patient was ...

The potential benefits of low-molecular-weight heparins in cancer patients

Journal of Hematology and Oncology — Thu, 14 Jan 2010 00:00:00 +0100

Cancer patients are at increased risk of venous thromboembolism due to a range of factors directly related to their disease and its treatment. Given the high incidence of post-surgical venous thromboembolism in cancer patients and the poor outcomes associated with its development, thromboprophylaxis is warranted. A number of evidence-based guidelines delineate anticoagulation regimens for venous thromboembolism treatment, primary and secondary prophylaxis, and long-term anticoagulation in cancer patients. However, many give equal weight to several different drugs and do not make specific recommendations regarding duration of therapy. In terms of their efficacy and safety profiles, practicality of use, and cost-effectiveness the low-molecular-weight heparins are at least comparable to, and ...

Leser-Trelat syndrome in patients affected by six multiple metachronous primitive cancers

Journal of Hematology and Oncology — Mon, 11 Jan 2010 00:00:00 +0100

Leser-Trelat syndrome is characterized by the eruptive appearance of multiple seborrheic keratoses in association with underlying malignant disease. Usually, the sign of Leser-Trelat is associated with adenocarcinoma, most frequently of the colon, breast, or stomach, but also of the lung, kidney, liver, and pancreas. Herein, we present a case that we believe is the first report of the sign of Leser-Trelat in association with occult gastric adenocarcinoma and the anamnestic oncologic history of five other multiple primitive cancers. Epidermal growth factor receptor (EGFR) immunohistochemical expression analysis of multiple seborrheic keratoses revealed an intense membranous staining in the basal keratinocytes and in all the upper epidermal layers. Patients with the sign of Leser-Trelat shou...

Treatment outcome of thalidomide based regimens in newly diagnosed and relapsed/ refractory non- transplant multiple myeloma patients: a single center experience from Thailand

Journal of Hematology and Oncology — Tue, 05 Jan 2010 00:00:00 +0100

Conclusions: Prolonged thalidomide therapy enhanced survival rate and less frequently developed serious toxicity in non- transplant multiple myeloma patients. (Source: Journal of Hematology and Oncology)

Autonomous growth potential of leukemia blast cells is associated with poor prognosis in human acute leukemias

Journal of Hematology and Oncology — Tue, 29 Dec 2009 00:00:00 +0100

We have described a severe combined immunodeficiency (SCID) mouse model that permits the subcutaneous growth of primary human acute leukemia blast cells into a measurable subcutaneous nodule which may be followed by the development of disseminated disease. Utilizing the SCID mouse model, we examined the growth potential of leukemic blasts from 133 patients with acute leukemia, (67 acute lymphoblastic leukemia (ALL) and 66 acute myeloid leukemia (AML)) in the animals after subcutaneous inoculation without conditioning treatment. The blasts displayed three distinct growth patterns: "aggressive", "indolent", or "no tumor growth". Out of 133 leukemias, 46 (34.5%) displayed an aggressive growth pattern, 14 (10.5%) displayed an indolent growth pattern and 73 (55.0%) did not grow in SCID mice. Th...

New targets for the treatment of follicular lymphoma

Journal of Hematology and Oncology — Wed, 23 Dec 2009 00:00:00 +0100

The last two decades have witnessed striking advances in our understanding of the biological factors underlying the development of Follicular lymphoma (FL). Development of newer treatment strategies have improved the outlook for many individuals with these disorders; however, with these advances come new questions. Given the long-term survival of patients with FL, drugs with favourable side-effect profile and minimal long-term risks are desired. FL is incurable with current treatment modalities. It often runs an indolent course with multiple relapses and progressively shorter intervals of remission. The identification of new targets and development of novel targeted therapies is imperative to exploit the biology of FL while inherently preventing relapse and prolonging survival. This review...

Routine use of ancillary investigations in staging diffuse large B-cell lymphoma improves the International Prognostic Index (IPI)

Journal of Hematology and Oncology — Sun, 22 Nov 2009 00:00:00 +0100

Conclusions: Improved bone marrow staging using flow cytometry and immunohistochemistry improves the predictive value of the IPI in patients with DLBCl and should be performed routinely in all cases. (Source: Journal of Hematology and Oncology)

Multiple Myeloma Involving Skin and Pulmonary Parenchyma after Autologous Stem Cell Transplantation

Journal of Hematology and Oncology — Fri, 13 Nov 2009 00:00:00 +0100

Pulmonary involvement and skin involvement are rare complications of plasma cell neoplasms. Here we describe what may be the first reported case of a patient with relapse in both of these sites following autologous peripheral blood stem cell transplantation. (Source: Journal of Hematology and Oncology)

The occurrence and management of fluid retention associated with TKI therapy in CML, with a focus on dasatinib

Journal of Hematology and Oncology — Thu, 12 Nov 2009 00:00:00 +0100

Tyrosine kinase inhibitors (TKIs) like dasatinib and nilotinib are indicated as second-line treatment for chronic myeloid leukemia resistant or intolerant to the current first-line TKI imatinib. These are agents are well tolerated, but potent and as such should be monitored for potentially serious side-effects like fluid retention and pleural effusions. Here we present key clinical trial data and safety considerations for all FDA approved TKIs in context for effective management of fluid retention and pleural effusions. Altering the dasatinib regimen from 70 mg twice daily to 100 mg daily reduces the risk of pleural effusion for patients taking dasatinib. Should pleural effusion develop, dasatinib should be interrupted until the condition resolves. Patients with a history of pleural effusi...

Genomic profiling of plasmablastic lymphoma using array comparative genomic hybridization (aCGH) : revealing significant overlapping genomic lesions with diffuse large B-cell lymphoma

Journal of Hematology and Oncology — Thu, 12 Nov 2009 00:00:00 +0100

Conclusions: To the best of our knowledge, the current study represents the first genomic exploration of PL. The genomic aberration pattern of PL appears to be more similar to that of DLBCL (AIDS-related or non AIDS-related) than to PCM. Our findings suggest that PL may remain best classified as a subtype of DLBCL at least at the genome level. (Source: Journal of Hematology and Oncology)

Targeting tumorigenesis: development and use of mTOR inhibitors in cancer therapy

Journal of Hematology and Oncology — Tue, 27 Oct 2009 00:00:00 +0100

The mammalian target of rapamycin (mTOR) is an intracellular serine/threonine protein kinase positioned at a central point in a variety of cellular signaling cascades. The established involvement of mTOR activity in the cellular processes that contribute to the development and progression of cancer has identified mTOR as a major link in tumorigenesis. Consequently, inhibitors of mTOR, including temsirolimus, everolimus, and ridaforolimus (formerly deforolimus) have been developed and assessed for their safety and efficacy in patients with cancer. Temsirolimus is an intravenously administered agent approved by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMEA) for the treatment of advanced renal cell carcinoma (RCC). Everolimus is an oral agent that has recen...

The transplant iron score as a predictor of stem cell transplant survival

Journal of Hematology and Oncology — Fri, 23 Oct 2009 23:00:00 +0100

Recent studies have suggested that the presence of iron overload prior to stem cell transplantation is associated with decreased survival. Within these studies, the criteria used to define iron overload have varied considerably. Given the lack of consensus regarding the definition of iron overload in the transplant setting, we sought to methodically examine iron status among transplant patients. We studied 78 consecutive patients at risk for transfusion-related iron overload (diagnoses included AML, ALL, MDS, and aplastic anemia) who received either autologous or allogeneic stem cell transplant. Multiple measures of iron status were collected prior to transplantation and examined for their association with survival. Using this data, three potentially prognostic iron measures were identifie...

Plasma protein C levels in immunocompromised septic patients are significantly lower than immunocompetent septic patients: a prospective cohort study

Journal of Hematology and Oncology — Sun, 18 Oct 2009 23:00:00 +0100

Conclusion: Protein C levels were significantly lower in immunocompromised patients when compared to immunocompetent patients in severe sepsis and sepsis categories. Our study suggests a plausible role for APC in severely septic immunocompromised patients which need further elucidation. (Source: Journal of Hematology and Oncology)

Two successful pregnancies in a woman with chronic myeloid leukemia exposed to nilotinib during the first trimester of her second pregnancy: case study

Journal of Hematology and Oncology — Mon, 05 Oct 2009 23:00:00 +0100

We report a 30-year-old woman with chronic myeloid leukemia who became pregnant twice successfully. Philadelphia-positive CML in its chronic phase was diagnosed at 16 weeks of her first gestation. At that time, she received no treatment throughout her pregnancy. At 38 weeks of gestation, a normal infant was delivered by cesarean section. At six weeks postpartum, the patient underwent imatinib mesylate therapy but she could not tolerate the treatment. The treatment was then changed to nilotinib at 400 mg orally b.i.d. Two years later, she became pregnant again while she was on nilotinib 200 mg b.i.d. The unplanned pregnancy was identified during her 7.4 weeks of gestation. Because the patient elected to continue her pregnancy, nilotinib was stopped immediately, and no further treatment was ...

Skeletal Plasmacytoma: Progression of disease and impact of local treatment; an analysis of SEER database

Journal of Hematology and Oncology — Wed, 23 Sep 2009 23:00:00 +0100

DiscussionPlasmacytoma consists of two cohorts of patients with different overall survival; those patients that do not progress to systemic disease and those that develop myeloma. Age > 60 years is associated with disease progression. Identifying patients with systemic disease early in the treatment will permit aggressive and novel treatment strategies to be implemented. (Source: Journal of Hematology and Oncology)

Complications of Evans' syndrome in an infant with hereditary spherocytosis: a case report

Journal of Hematology and Oncology — Wed, 09 Sep 2009 23:00:00 +0100

Hereditary spherocytosis (HS) is a genetic disorder of the red blood cell membrane that is characterized clinically by anemia, jaundice and splenomegaly. Evans' syndrome is a clinical syndrome characterized by autoimmune hemolytic anemia (AIHA) accompanied by immune thrombocytopenic purpura (ITP). It results from a malfunction of the immune system that produces multiple autoantibodies specific for red blood cells and platelets (and sometimes other targets). Thus, HS and Evans' syndrome differ in their pathophysiological mechanisms. Here, we report the unusual case of an infant who had both of these diseases concurrently. Possible explanations of this unexpected situation are discussed. (Source: Journal of Hematology and Oncology)

Lymphomatoid granulomatosis masquerading as interstitial pneumonia in a 66-year-old man: a case report and review of literature

Journal of Hematology and Oncology — Thu, 03 Sep 2009 23:00:00 +0100

We report a case of rapid respiratory deterioration in a 66-year-old man with clinical presentation, chest radiography, pulmonary function testing and high resolution computed tomography (HRCT) findings consistent with idiopathic interstitial pneumonia, but very poor response to antibiotics and steroids. Lung biopsy showed histopathology consistent with LG that was confirmed by a positive in situ hybridization for Epstein - Barr virus encoded RNA (EBER). The patient was treated with rituximab and combination chemotherapy and showed significant initial clinical improvement with gradual resolution of abnormal findings on imaging. However, the patient developed pancytopenia as a complication of chemotherapy and died secondary to septic shock and renal failure that were refractory to medical m...

Emerging role of Garcinol, the antioxidant chalcone from Garcinia indica Choisy and its synthetic analogs

Journal of Hematology and Oncology — Tue, 01 Sep 2009 23:00:00 +0100

Garcinol, harvested from Garcinia indica, has traditionally been used in tropical regions and appreciated for centuries; however its biological properties are only beginning to be elucidated. There is ample data to suggest potent antioxidant properties of this compound which have been used to explain most of its observed biological activities. However, emerging evidence suggests that garcinol could be useful as an anti-cancer agent, and it is increasingly being realized that garcinol is a pleiotropic agent capable of modulating key regulatory cell signaling pathways. Here we have summarized the progress of our current research knowledge on garcinol and its observed biological activities. We have also provided an explanation of observed properties based on its chemical structure and provide...

Different altered stage correlative expression of high abundance acute-phase proteins in sera of patients with epithelial ovarian carcinoma

Journal of Hematology and Oncology — Wed, 26 Aug 2009 23:00:00 +0100

Conclusion: Our results highlight the potential prognostic significance of selective high abundance serum APPs in patients with EOCa. (Source: Journal of Hematology and Oncology)

Mechanism of action of lenalidomide in hematological malignancies

Journal of Hematology and Oncology — Tue, 11 Aug 2009 23:00:00 +0100

Immunomodulatory drugs lenalidomide and pomalidomide are synthetic compounds derived by modifying the chemical structure of thalidomide to improve its potency and reduce its side effects. . Lenalidomide is a 4-amino-glutamyl analogue of thalidomide that lacks the neurologic side effects of sedation and neuropathy and has emerged as a drug with activity against various hematological and solid malignancies. It is approved by FDA for clinical use in myelodysplastic syndromes with deletion of chromosome 5q and multiple myeloma. Lenalidomide has been shown to be an immunomodulator, affecting both cellular and humoral limbs of the immune system. It has also been shown to have anti-angiogenic properties. Newer studies demonstrate its effects on signal transduction that can partly explain its sele...

Phenotype and functional evaluation of ex vivo generated antigen-specific immune effector cells with potential for therapeutic applications

Journal of Hematology and Oncology — Wed, 05 Aug 2009 23:00:00 +0100

Ex vivo activation and expansion of lymphocytes for adoptive cell therapy has demonstrated great success. To improve safety and therapeutic efficacy, increased antigen specificity and reduced non-specific response of the ex vivo generated immune cells are necessary. Here, using a complete protein-spanning pool of pentadecapeptides of the latent membrane protein 2A (LMP2A) of Epstein-Barr virus (EBV), a weak viral antigen which is associated with EBV lymphoproliferative diseases, we investigated the phenotype and function of immune effector cells generated based on IFN-gamma or CD137 activation marker selection and dendritic cell (DC) activation. These ex vivo prepared immune cells exhibited a donor- and antigen-dependent T cell response; the IFN-gamma-selected immune cells displayed a dono...

Complete pathological response in a patient with multiple liver metastases from colon cancer treated with Folfox-6 chemotherapy plus bevacizumab: a case report

Journal of Hematology and Oncology — Wed, 05 Aug 2009 23:00:00 +0100

The complete pathological response after primary chemotherapy could represent an important prognostic factor in patients affected by colorectal liver metastases.In recent studies, increasing pCR seems to be correlated with longer overall survival periods and it is recognized as an important prognostic factor in patients treated with pre-operative chemotherapy.The correlation of radiological information on residual neoplastic disease after neoadjuvant treatment, obtained with CT and PET, has to be evaluated; in fact the complete disappearance of liver metastasis on radiological imaging does not always mean a complete disappearance of tumor tissue on histological examination; when it is documented with surgical procedures and confirmed by pathologist's examination, we can consider the comple...

A homoharringtonine-based induction regimen for the treatment of elderly patients with acute myeloid leukemia: a single center experience from China

Journal of Hematology and Oncology — Wed, 29 Jul 2009 23:00:00 +0100

Conclusion: HA is a suitable induction regimen for elderly patients with AML, with relatively low toxicity and reasonable response rate. (Source: Journal of Hematology and Oncology)

ABT-869, a promising multi-targeted tyrosine kinase inhibitor: from bench to bedside

Journal of Hematology and Oncology — Wed, 29 Jul 2009 23:00:00 +0100

Tyrosine Kinase Inhibitors (TKI) have significantly changed the landscape of current cancer therapy. Understanding of mechanisms of aberrant TK signaling and strategies to inhibit TKs in cancer, further promote the development of novel agents.ABT-869, a novel ATP-competitive receptor tyrosine kinase inhibitor is a potent inhibitor of members of the vascular endothelial growth factor (VEGF) and platelet derived growth factor (PDGF) receptor families. ABT-869 showed potent antiproliferative and apoptotic properties in vitro and in animal cancer xenograft models using tumor cell lines that were "addicted" to signaling of kinases targeted by ABT-869. When given together with chemotherapy or mTOR inhibitors, ABT-869 showed at least additive therapeutic effects. The phase I trial for ABT-869 wa...

Vorinostat in solid and hematologic malignancies

Journal of Hematology and Oncology — Sun, 26 Jul 2009 23:00:00 +0100

Vorinostat (Zolinza(R)), a histone deacetylase inhibitor, was approved by the US Food and Drug Administration in October 2006 for the treatment of cutaneous manifestations in patients with cutaneous T-cell lymphoma who have progressive, persistent or recurrent disease on or following two systemic therapies. This review summarizes evidence on the use of vorinostat in solid and hematologic malignancies and collated tolerability data from the vorinostat clinical trial program. Pooled vorinostat clinical trial data from 498 patients with solid or hematologic malignancies show that vorinostat was well tolerated as monotherapy or combination therapy. The most commonly reported drug-related adverse events (AEs) associated with monotherapy (n = 341) were fatigue (61.9%), nausea (55.7%), diarrhea (...

Gender and ethnic differences in chronic myelogenous leukemia prognosis and treatment response: a single-institution retrospective study

Journal of Hematology and Oncology — Thu, 23 Jul 2009 23:00:00 +0100

Conclusions: Female CML patients at LAC+USC Medical Center present with more significant adverse pre-treatment prognostic factors compared to men, but achieve comparable outcomes. Hispanic patients present with lower risk profile CML and achieve better treatment responses compared to non-Hispanic patients as a whole; these ethnic differences are no longer significant when statistical analysis is limited to patients given imatinib as first-line therapy. Our patients achieve response rates inferior to those of large-scale national studies. This constellation of findings has not been reported in previous studies, and is likely reflective of a unique patient population. (Source: Journal of Hematology and Oncology)

Update in the management of chronic lymphocytic leukemia

Journal of Hematology and Oncology — Sun, 19 Jul 2009 23:00:00 +0100

Advances in the treatment of chronic lymphocytic leukemia (CLL) have improved initial overall response (OR) rates, complete response (CR) rates and progression free survival (PFS). Despite these advances, CLL remains incurable with standard therapies. Thus, there remains a need for more effective therapies in both the upfront and relapsed setting, particularly for patients with high-risk cytogenetic abnormalities such as del(11q22) and del(17p13). The 2008 American Society of Hematology (ASH) Annual Meeting featured several presentations which highlighted the ongoing clinical advances in CLL. The benefit of adding rituximab to purine analog therapy in the upfront setting was demonstrated by a large randomized study which showed that the addition of rituximab to fludarabine and cyclophospha...

RIZ1 is potential CML tumor suppressor that is down-regulated during disease progression

Journal of Hematology and Oncology — Mon, 13 Jul 2009 23:00:00 +0100

Conclusions: RIZ1 is a candidate tumor suppressor gene whose expression is decreased in blast crisis. Loss of RIZ1 activity results in decreased apoptosis and differentiation and enhanced proliferation. Together these results suggest that loss of RIZ1 expression will lead to an increase in myeloid blast cell population resulting in CML progression. (Source: Journal of Hematology and Oncology)

Co-existence of acute myeloid leukemia with multilineage dysplasia and Epstein-Barr virus-associated T-cell lymphoproliferative disorder in a patient with rheumatoid arthritis

Journal of Hematology and Oncology — Mon, 29 Jun 2009 23:00:00 +0100

We here report a case of rheumatoid arthritis (RA) with acute myeloid leukemia with multilineage dysplasia (AML-MLD) and Epstein-Barr virus (EBV)-associated T-cell lymphoproliferative disorder (T-LPD). A 64-year-old healthy man suffered from arthralgia, and was ultimately diagnosed with RA based on bilateral hand X-rays showing mild swelling and destruction of the MP and PIP joints. Since non-steroidal anti-inflammatory drugs were not effective, prednisolone and bucillamine were administered. After 4 months, his pancytopenia gradually progressed, and bone marrow (BM) examination revealed the presence of AML-MLD. A chemotherapeutic drug regimen including low-dose cytarabine led to nearly complete remission, but several weeks later, high fever and dyspnea suddenly appeared. Computer tomograp...

Adult B lymphoblastic leukaemia / lymphoma with hypodiploidy (-9) and a novel chromosomal translocation t(7;12)(q22;p13) presenting with severe eosinophilia - case report and review of literature

Journal of Hematology and Oncology — Sat, 20 Jun 2009 23:00:00 +0100

We describe a rare presentation of acute lymphoblastic leukemia in a young adult male who had vague and minimal symptoms with mild splenomegaly. There was severe eosinophilia along with absence of blasts in the peripheral blood, and 40% blasts with increase in eosinophils in the bone marrow. The blasts were positive for common precursor B cell markers on flow cytometry. The patient had a unique cytogenetic abnormality t(7;12)(q22;p13),-9, not previously described in acute lymphoblastic leukemia. He was categorized as poor risk due to failure to achieve complete remission after induction with UK ALL XII chemotherapy. (Source: Journal of Hematology and Oncology)

The effects of beta-glucan on human immune and cancer cells

Journal of Hematology and Oncology — Wed, 10 Jun 2009 04:00:00 +0100

Non-prescriptional use of medicinal herbs among cancer patients is common around the world. The alleged anti-cancer effects of most herbal extracts are mainly based on studies derived from in vitro or in vivo animal experiments. The current information suggests that these herbal extracts exert their biological effect either through cytotoxic or immunomodulatory mechanisms. One of the active compounds responsible for the immune effects of herbal products is in the form of complex polysaccharides known as beta-glucans. beta-glucans are ubiquitously found in both bacterial or fungal cell walls and have been implicated in the initiation of anti-microbial immune response. Based on in vitro studies, beta-glucans act on several immune receptors including Dectin-1, complement receptor (CR3) and TL...

Identification of circulating tumour cells in early stage breast cancer patients using multi-marker immunobead RT-PCR

Journal of Hematology and Oncology — Fri, 05 Jun 2009 04:00:00 +0100

Conclusions: Multi-marker immunobead RT-PCR analysis of peripheral blood is a robust assay that is capable of detecting circulating tumour cells in early stage breast cancer patients. (Source: Journal of Hematology and Oncology)

Molecular prognostic markers for adult acute myeloid leukemia with normal cytogenetics

Journal of Hematology and Oncology — Tue, 02 Jun 2009 04:00:00 +0100

Acute myeloid leukemia (AML) is a heterogenous disorder that results from a block in the differentiation of hematopoietic progenitor cells along with uncontrolled proliferation. In approximately sixty percent of cases, specific recurrent chromosomal aberrations can be identified by modern cytogenetic techniques. This cytogenetic information is the single most important tool to classify patients at their initial diagnosis into three prognostic categories: favorable, intermediate, and poor risk. Currently, favorable risk AML patients are usually treated with contemporary chemotherapy while poor risk AML patients receive allogeneic stem cell transplantation if suitable stem cell donors exist. The largest subgroup of AML patients (approximately forty percent) have no identifiable cytogenetic a...

New clinical developments in histone deacetylase inhibitors for epigenetic therapy of cancer

Journal of Hematology and Oncology — Mon, 01 Jun 2009 04:00:00 +0100

DNA methylation and histone acetylation are two well known epigenetic chromatin modifications. Epigenetic agents leading to DNA hypomethylation and histone hyperacetylation have been approved for treatment of hematological disorders. The first histone deacetylase inhibitor, vorinostat, has been licensed for cutaneous T cell lymphoma treatment. More than 11 new epigenetic agents are in various stages of clinical development for therapy of multiple cancer types. In this review we summarize novel histone deacetylase inhibitors and new regimens from clinical trials for epigenetic therapy of cancer. (Source: Journal of Hematology and Oncology)

Temozolomide and cisplatin in relapsed/refractory acute leukemia

Journal of Hematology and Oncology — Fri, 22 May 2009 04:00:00 +0100

Cisplatin depletes MGMT and increases the sensitivity of leukemia cells to temozolomide. We performed a phase I study of cisplatin and temozolomide in patients with relapsed and refractory acute leukemia. Fifteen patients had AML, 3 had ALL, and 2 had biphenotypic leukemia. The median number of prior chemotherapy regimens was 3 (1-5). Treatment was well tolerated up to the maximal doses of temozolomide 200 mg/m2/d times 7 days and cisplatin 100 mg/m2 on day 1. There was one complete remission in this heavily pretreated patient population. Five of 20 (25%) patients demonstrated a significant reduction in bone marrow blasts. (Source: Journal of Hematology and Oncology)

Phase 1-2a multicenter dose-escalation study of ezatiostat hydrochloride liposomes for injection (Telintra(R), TLK199), a novel glutathione analog prodrug in patients with myelodysplastic syndrome

Journal of Hematology and Oncology — Wed, 13 May 2009 04:00:00 +0100

Conclusions: Phase 2 studies of ezatiostat hydrochloride liposomes for injection in MDS are supported by the tolerability and HI responses observed. An oral formulation of ezatiostat hydrochloride tablets is also in phase 2 clinical development. (Source: Journal of Hematology and Oncology)

Treatment of multicentric Castleman's Disease accompanying multiple myeloma with bortezomib: a case report

Journal of Hematology and Oncology — Tue, 28 Apr 2009 04:00:00 +0100

Multicentric Castleman's disease (MCD) is a rare lymphoproliferative disorder of unknown etiology and characterized by various clinical manifestations and multiple organ involvement. It has been reported in association with POEMS syndrome and can progress to Kaposi's sarcoma or malignant lymphoma. The disease runs a more aggressive course and a poor prognosis. Optimal therapies have not been well established up to now. We here reported a case of rare MCD complicated with multiple myeloma who received bortezomib and achieved very good remission. To our knowledge, this is the first report on MCD in the setting of multiple myeloma with good response to bortezomib. (Source: Journal of Hematology and Oncology)

Individualized Therapies in Colorectal Cancer: KRAS as a Marker for Response to EGFR-targeted Therapy

Journal of Hematology and Oncology — Wed, 22 Apr 2009 04:00:00 +0100

Individualized therapies that are tailored to a patient's genetic composition will be of tremendous value for treatment of cancer. Recently, Kirsten ras (KRAS) status has emerged as a predictor of response to epidermal growth factor receptor (EGFR) targeted therapies. In this article, we will discuss targeted therapies for CRC based on EGFR signaling pathway and review published data about the potential usefulness of KRAS as a biological marker for response to these therapies. Results from relevant studies published since 2005 and unpublished results presented at national meetings were retrieved and summarized. These studies reflected response (or lack of response) to EGFR-targeted therapies in patients with metastatic CRC as a function of KRAS status. It has become clear that patients wit...

Serum proteomic profiling and haptoglobin polymorphisms in patients with GVHD after allogeneic hematopoietic cell transplantation

Journal of Hematology and Oncology — Mon, 20 Apr 2009 04:00:00 +0100

In this study, quantitative serum Hp levels were shown to be related to cGVHD development. Further, the data suggest the possibility that specific Hp polymorphisms may be associated with cGVHD development and warrant further investigation. (Source: Journal of Hematology and Oncology)

Treatment of malignant tumors of the skull base with multi-session radiosurgery

Journal of Hematology and Oncology — Thu, 02 Apr 2009 04:00:00 +0100

Conclusion: Our experience suggests that multi-session radiosurgery for the treatment of malignant skull base tumors is comparable to other radiosurgical techniques in progression-free survival, local tumor control, and adverse effects. (Source: Journal of Hematology and Oncology)

Induction of endogenous gamma-globin gene expression with decoy oligonucleotide targeting Oct-1 transcription factor consensus sequence

Journal of Hematology and Oncology — Fri, 27 Mar 2009 04:00:00 +0100

Human beta-globin disorders are relatively common genetic diseases cause by mutations in the beta-globin gene. Increasing the expression of the gamma-globin gene has great benefits in reducing complications associated with these diseases. The Oct-1 transcription factor is involved in the transcriptional regulation of the gamma-globin gene. The human gamma-globin genes (both A-gamma and G-gamma-globin genes) carry three Oct-1 transcription factor consensus sequences within their promoter regions. We have studied the possibility of inducing gamma-globin gene expression using decoy oligonucleotides that target the Oct-1 transcription factor consensus sequence. A double-stranded 22bp decoy oligonucleotide containing the Oct-1 consensus sequence was synthesized. The results obtained from our in...

R-CHOP versus R-CVP in the treatment of follicular lymphoma: a meta-analysis and critical appraisal of current literature

Journal of Hematology and Oncology — Tue, 24 Mar 2009 04:00:00 +0100

Conclusion: Both R-CHOP and R-CVP protocols achieve excellent overall response. In patients with known cardiac history, omission of anthracyclines is reasonable and R-CVP provides a competitive CR rate. In younger patients with FL where cumulative cardio-toxicity may be of importance in the long term and in whom future stem cell transplantation is an option, again R-CVP may be a more appealing option. (Source: Journal of Hematology and Oncology)

Long term survivors with metastatic pancreatic adenocarcinoma treated with gemcitabine: a retrospective analysis

Journal of Hematology and Oncology — Mon, 16 Mar 2009 04:00:00 +0100

Conclusion: A subgroup of patients with metastatic pancreatic cancer has prolonged survival after treatment with gemcitabine. Only bilirubin and CA 19-9 levels were predictive of longer survival in this population. Further analysis of potential prognostic and predictive markers of response to treatment and survival are needed. (Source: Journal of Hematology and Oncology)

An unusual presentation of precursor T cell lymphoblastic leukemia/lymphoma with cholestatic jaundice: case report

Journal of Hematology and Oncology — Thu, 12 Mar 2009 04:00:00 +0100

Conclusion: Our case illustrates an unusual presentation of hematological malignancies as cholestatic jaundice. It also indicates the non-specific nature of CA 19-9 for pancreaticobiliary malignancies. It is the first case report of neoplastic precursor T cell lymphoblasts with unusual expression of synaptophysin. Tissue biopsy with thorough immunohistochemistry is required to differentiate precursor T-ALL/T-LBL from thymoma and small cell carcinoma. (Source: Journal of Hematology and Oncology)

Updates in Gastrointestinal Oncology – insights from the 2008 44th annual meeting of the American Society of Clinical Oncology

Journal of Hematology and Oncology — Mon, 23 Feb 2009 05:00:00 +0100

We have reviewed the pivotal presentations rcelated to colorectal cancer (CRC) and other gastrointestinal malignancies from 2008 annual meeting of the American Society of Clinical Oncology (ASCO). We have discussed the scientific findings and the impact on practice guidelines and ongoing clinical trials. The report on KRAS status in patients with metastatic CRC receiving epidermal growth factor receptor (EGFR) targeted antibody treatment has led to a change in National Comprehensive Cancer Network guideline that recommends only patients with wild-type KRAS tumor should receive this treatment. The results of double biologics (bevacizumab and anti-EGFR antibody) plus chemotherapy as first-line treatment in patients with metastatic CRC has shown a worse outcome than bevacizumab-based regimen....

Updates in Gastrointestinal Oncology - insights from the 2008 44th annual meeting of the American Society of Clinical Oncology

Journal of Hematology and Oncology — Mon, 23 Feb 2009 05:00:00 +0100

We have reviewed the pivotal presentations related to colorectal cancer (CRC) and other gastrointestinal malignancy from 2008 annual meeting of the American Society of Clinical Oncology (ASCO). We have discussed the scientific findings and the impact on practice guidelines and ongoing clinical trials. The report on KRAS status in patients with metastatic CRC receiving epidermal growth factor receptor (EGFR) targeted antibody treatment has led to a change in National Comprehensive Cancer Network guideline that recommends only patients with wild-type KRAS tumor should receive this treatment. The results of double biologics (bevacizumab and anti-EGFR antibody) plus chemotherapy as 1st-line treatment in patients with metastatic CRC has shown a worse outcome than bevacizumab-based regimen. Micr...

New dosing schedules of dasatinib for CML and adverse event management

Journal of Hematology and Oncology — Mon, 23 Feb 2009 05:00:00 +0100

Resistance to imatinib in patients with chronic myelogenous leukemia (CML) or Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) has emerged as a significant clinical issue. Dasatinib is a tyrosine kinase inhibitor that has 325-fold greater in vitro activity against native BCR-ABL (breakpoint cluster region-Abelson leukemia virus) compared with imatinib and can overcome primary (intrinsic) and secondary (acquired) imatinib resistance. Here, we review the clinical profile of dasatinib in imatinib-resistant and -intolerant patients and share clinical approaches for managing adverse events (AEs) to ensure maximum patient benefit. References were obtained through literature searches on PubMed as well as from the Proceedings of Annual Meetings of the American Society of Cli...

Radiation produces differential changes in cytokine profiles in radiation lung fibrosis sensitive and resistant mice

Journal of Hematology and Oncology — Mon, 02 Feb 2009 05:00:00 +0100

Conclusions: Radiation induced earlier and greater temporal changes in multiple cytokines in the pulmonary fibrosis sensitive mice. Positive correlation between blood and tissue levels suggests that blood may be used as a surrogate marker for tissue. (Source: Journal of Hematology and Oncology)