Union for International Cancer Control International Session: healthcare economics: the significance of the UN Summit non-communicable diseases political declaration in Asia.

The Japan National Committee for the Union for International Cancer Control (UICC) and UICC-Asia Regional Office (ARO) organized an international session as part of the official program of the 71st Annual Meeting of the Japanese Cancer Association to discuss the topic "Healthcare Economics: The Significance of the UN Summit non-communicable diseases (NCDs) Political Declaration in Asia." The presenters and participants discussed the growing cost of cancer in the Asian region and the challenges that are faced by the countries of Asia, all of which face budgetary and other systemic constraints in tackling and controlling cancer in the region. The session benefited from the participation of various stakeholders, including cancer researchers and representatives of the pharmaceutical industry.

Integrative analysis reveals an outcome-associated and targetable pattern of p53 and cell cycle deregulation in diffuse large B cell lymphoma.

Diffuse large B cell lymphoma (DLBCL) is a clinically and biologically heterogeneous disease with a high proliferation rate. By integrating copy number data with transcriptional profiles and performing pathway analysis in primary DLBCLs, we identified a comprehensive set of copy number alterations (CNAs) that decreased p53 activity and perturbed cell cycle regulation. Primary tumors either had multiple complementary alterations of p53 and cell cycle components or largely lacked these lesions.

Phase II study of intensive post-remission chemotherapy and stem cell transplantation for adult acute lymphoblastic leukemia and lymphoblastic lymphoma: Japan Clinical Oncology Group Study, JCOG9402.

Objective: To evaluate the efficacy and safety of intensive post-remission chemotherapy for untreated patients aged 15-69 years with adult acute lymphoblastic leukemia and lymphoblastic lymphoma in a multicenter Phase II study.

Methods: The chemotherapy regimen consisted of induction, post-remission and maintenance for 2 years. The primary endpoint was 5-year progression-free survival, and secondary endpoints included complete remission rate, overall survival and adverse events.

Viral induction and targeted inhibition of galectin-1 in EBV+ posttransplant lymphoproliferative disorders.

Posttransplant lymphoproliferative disorders (PTLDs) are potentially fatal, EBV-driven B-cell malignancies that develop in immunocompromised solid organ or hematopoietic stem cell recipients. In PTLD, the expression of EBV proteins, including latent membrane protein 1 (LMP1) and LMP2A, viral immune evasion strategies, and impaired host immune surveillance foster the proliferation of EBV-transformed B cells. Current PTLD treatment strategies include reduction of immunosuppression, which increases the risk of graft rejection, anti-CD20 treatment, combination chemotherapy, and administration of EBV-specific cytotoxic T cells.

Integrative analysis reveals selective 9p24.1 amplification, increased PD-1 ligand expression, and further induction via JAK2 in nodular sclerosing Hodgkin lymphoma and primary mediastinal large B-cell lymphoma.

Classical Hodgkin lymphoma (cHL) and mediastinal large B-cell lymphoma (MLBCL) are lymphoid malignancies with certain shared clinical, histologic, and molecular features. Primary cHLs and MLBCLs include variable numbers of malignant cells within an inflammatory infiltrate, suggesting that these tumors escape immune surveillance. Herein, we integrate high-resolution copy number data with transcriptional profiles and identify the immunoregulatory genes, PD-L1 and PD-L2, as key targets at the 9p24.

MLL-rearranged B lymphoblastic leukemias selectively express the immunoregulatory carbohydrate-binding protein galectin-1.

Purpose: Patients with mixed lineage leukemia (MLL)-rearranged B-lymphoblastic leukemias (B-ALL) have an unfavorable prognosis and require intensified treatment. Multiple MLL fusion partners have been identified, complicating the diagnostic evaluation of MLL rearrangements. We analyzed molecular markers of MLL rearrangement for use in rapid diagnostic assays and found the immunomodulatory protein, Galectin-1 (Gal-1), to be selectively expressed in MLL-rearranged B-ALL.

No evidence for the JAK2 (V617F) or JAK2 exon 12 mutations in primary mediastinal large B-cell lymphoma.

Dysregulated JAK2 signaling has been shown to play a significant role in the pathogenesis of myeloproliferative disorders. Recently, our work comparing gene expression signatures of primary mediastinal large B-cell lymphomas (PMLBCL) versus nodal diffuse large B-cell lymphomas revealed a relative increase in JAK2 transcripts in the former, suggesting a role for increased JAK2 signaling in a subset of these tumors. Given the likelihood of increased JAK2 signaling in PMLBCL, we sought to determine whether JAK2 activating mutations were an alternative mechanism for increased JAK2 signaling in untreated PMLBCLs.

The heat shock protein 90 inhibitor IPI-504 induces apoptosis of AKT-dependent diffuse large B-cell lymphomas.

Heat shock protein 90 (HSP90) is a molecular chaperone that stabilizes critical client proteins in multiple cancers. Gene expression profiling was utilized to characterize HSP90 isoform expression in primary human diffuse large B-cell lymphomas (DLBCLs). HSP90 alpha and beta isoforms were differentially expressed in subsets of tumours defined by their transcriptional profiles.

Phase III study to evaluate the use of high-dose chemotherapy as consolidation of treatment for high-risk postoperative breast cancer: Japan Clinical Oncology Group study, JCOG 9208.

A randomized controlled trial was conducted to evaluate the efficacy of high-dose chemotherapy (HDC) as consolidation of the treatment of high-risk postoperative breast cancer. Patients under 56 years of age with stage I to IIIB breast cancer involving 10 or more axillary lymph nodes were eligible. The primary endpoint was relapse-free survival (RFS).

BH3 profiling identifies three distinct classes of apoptotic blocks to predict response to ABT-737 and conventional chemotherapeutic agents.

Cancer cells exhibit many abnormal phenotypes that induce apoptotic signaling via the intrinsic, or mitochondrial, pathway. That cancer cells nonetheless survive implies that they select for blocks in apoptosis. Identifying cancer-specific apoptotic blocks is necessary to rationally target them.

The AP1-dependent secretion of galectin-1 by Reed Sternberg cells fosters immune privilege in classical Hodgkin lymphoma.

Classical Hodgkin lymphomas (cHLs) contain small numbers of neoplastic Reed-Sternberg (RS) cells within an extensive inflammatory infiltrate that includes abundant T helper (Th)-2 and T regulatory (Treg) cells. The skewed nature of the T cell infiltrate and the lack of an effective host antitumor immune response suggest that RS cells use potent mechanisms to evade immune attack. In a screen for T cell-inhibitory molecules in cHL, we found that RS cells selectively overexpressed the immunoregulatory glycan-binding protein, galectin-1 (Gal1), through an AP1-dependent enhancer.

Phase II study of chemotherapy and stem cell transplantation for adult acute lymphoblastic leukemia or lymphoblastic lymphoma: Japan Clinical Oncology Group Study 9004.

Granulocyte colony-stimulating factor (G-CSF)-supported, post-remission chemotherapy (Cx) for adult acute lymphoblastic leukemia (ALL) or lymphoblastic lymphoma (LBL) was evaluated. One hundred and forty-three eligible patients (median age, 41 years) including 126 ALL and 17 LBL receiving induction Cx (vincristine, cyclophosphamide, prednisolone [PSL], doxorubicin, L-asparaginase, intrathecal-methotrexate [IT-MTX]) were analyzed. For patients achieving complete response (CR), two courses of post-remission Cx (course A of daunorubicin, cytosine arabinoside, vindesine, PSL plus IT-MTX; course B of mitoxantrone, etoposide, vincristine, PSL plus IT-MTX) with the use of G-CSF were repeated alternately; thereafter, maintenance Cx including MTX and 6-mercaptopurine was given for 2 years.

Protein tyrosine phosphatase receptor-type O truncated (PTPROt) regulates SYK phosphorylation, proximal B-cell-receptor signaling, and cellular proliferation.

The strength and duration of B-cell-receptor (BCR) signaling depends upon the balance between protein tyrosine kinase (PTK) activation and protein tyrosine phosphatase (PTP) inhibition. BCR-dependent activation of the SYK PTK initiates downstream signaling events and amplifies the original BCR signal. Although BCR-associated SYK phosphorylation is clearly regulated by PTPs, SYK has not been identified as a direct PTP substrate.

Complete donor chimaerism of Langerhans cells in lymph node early after allogeneic bone marrow transplantation.

Host-derived Langerhans cells (LCs) are crucial antigen-presenting cells that cause graft-vs.-host disease after allogeneic haematopoietic stem cell transplantation (HSCT). However, chimaerism of LCs after allogeneic HSCT is largely unknown in humans.

B-aggressive lymphoma family proteins have unique domains that modulate transcription and exhibit poly(ADP-ribose) polymerase activity.

BAL1 (B-aggressive lymphoma 1) was originally identified as a risk-related gene in diffuse large B-cell lymphoma. BAL1 encodes a nuclear protein with N-terminal macro domains and a putative C-terminal poly(ADP-ribose) polymerase (PARP) active site. Macro domains are sequences homologous to the non-histone region of histone macroH2A.

PBSC mobilization.

Intentional recruitment of hematopoietic stem cells from bone marrow to peripheral blood is a clinical process termed peripheral blood stem cell (PSBC) mobilization. Mobilized PSBC has replaced bone marrow as the preferred source of stem cells for patients undergoing high-dose chemotherapy because of rapid and durable engraftment and reconstitution of functional bone marrow. Although the mechanism involved in the process of PBSC mobilization by cytokines is largely unknown, granulocyte colony-stimulating factor (G-CSF) alone or chemotherapy combined with GCSF is used as a mobilizing agent in current clinical practice.

The BAL-binding protein BBAP and related Deltex family members exhibit ubiquitin-protein isopeptide ligase activity.

Members of the DTX (Deltex) family act as Notch signaling modifiers and may also regulate transcription through interactions with specific transcription factors. DTX proteins have a basic N terminus; a central proline-rich region; and a C-terminal RING finger domain, a motif often found in ubiquitin-protein isopeptide ligases (E3). Recently, we identified and characterized a unique diffuse large B-cell lymphoma risk-related gene named BAL (B aggressive lymphoma).

A dose-finding study of glycosylated G-CSF (Lenograstim) combined with CHOP therapy for stem cell mobilization in patients with non-Hodgkin's lymphoma.

Background: Peripheral blood stem cell (PBSC) reinfusion has been widely used for hematopoietic reconstitution after high-dose chemotherapy. However, the optimal dose of granulocyte colony-stimulating factor (G-CSF) for PBSC mobilization in combination with chemotherapy for autograft remains unknown.

Methods: To find the optimal dose of glycosylated G-CSF (lenograstim) for PBSC mobilization in combination with chemotherapy for aggressive non-Hodgkin's lymphoma (NHL), we conducted a dose-finding study on 43 newly diagnosed patients who had unfavorable prognostic factors.