Phase III study of bilayer sustained-release tramadol tablets in patients with cancer pain: a double-blind parallel-group, non-inferiority study with immediate-release tramadol capsules as an active comparator.

Purpose: We investigated whether twice-daily administration of a bilayer tablet formulation of tramadol (35% immediate-release [IR] and 65% sustained-release) is as effective as four-times-daily IR tramadol capsules for managing cancer pain.

Methods: This randomized, double-blind, double-dummy, active-comparator, non-inferiority study enrolled opioid-naïve patients using non-steroidal anti-inflammatory drugs or acetaminophen (paracetamol) to manage cancer pain and self-reported pain (mean value over 3 days ≥ 25 mm on a 100-mm visual analog scale [VAS]). Patients were randomized to either bilayer tablets or IR capsules for 14 days.

Retroperitoneal Bulky Histiocytic Sarcoma Successfully Treated with Induction Chemotherapy Followed by Curative Surgery.

Histiocytic sarcoma (HS) is a rare hematopoietic neoplasm. We report a patient with HS treated with induction chemotherapy followed by curative surgery. A 50-year-old man was referred to our hospital because of a retroperitoneal tumor.

Prognostic Factors and Outcomes of Adult-Onset Hemophagocytic Lymphohistiocytosis: A Retrospective Analysis of 34 Cases.

Adult-onset hemophagocytic lymphohistiocytosis (HLH) has features that are distinct from that of HLH in pediatric patients. The clinical records at the Japanese Red Cross Kumamoto Hospital were reviewed. We retrospectively analyzed 34 patients who fulfilled the diagnostic criteria of HLH-2004.

Successful use of extracorporeal membrane oxygenation for respiratory failure caused by mediastinal precursor T lymphoblastic lymphoma.

Precursor T lymphoblastic lymphoma (T-LBL) often manifests as a mediastinal mass sometimes compressing vital structures like vessels or large airways. This case was a 40-year-old male who developed T-LBL presenting as respiratory failure caused by mediastinal T-LBL. He presented with persistent life threatening hypoxia despite tracheal intubation.

Endoglin-targeted cancer therapy.

Vascular-targeting antiangiogenic therapy (VTAT) of cancer can be advantageous over conventional tumor cell targeted cancer therapy if an appropriate target is found. Our hypothesis is that endoglin (ENG; CD105) is an excellent target in VTAT. ENG is selectively expressed on vascular and lymphatic endothelium in tumors.

Anti-endoglin monoclonal antibodies are effective for suppressing metastasis and the primary tumors by targeting tumor vasculature.

Anti-metastatic activity of an antitumor agent is exceedingly important because metastasis is the primary cause of death for most solid cancer patients. In this report, we show that 3 anti-endoglin (ENG) monoclonal antibodies (mAbs) SN6a, SN6j and SN6k which define individually distinct epitopes of ENG of tumor vasculature are capable of suppressing tumor metastases in the multiple metastasis models. The metastasis models were generated by i.

Successful treatment with liposomal doxorubicin for widespread Kaposi's sarcoma and human herpesvirus-8 related severe hemophagocytic syndrome in a patient with acquired immunodeficiency syndrome.

Hemophagocytic syndrome (HPS) sometimes occurres in patients with acquired immunodeficiency syndrome (AIDS). Human herpesvirus-8 (HHV-8)/Kaposi's sarcoma (KS)-associated herpesvirus has so far been recognized as a trigger of HPS in immunosuppressed subject. We describe a 39-year-old man with AIDS who had widespread mucocutaneous and pulmonary KS and severe HPS.

Establishment of CD5 and CD10 double-positive mature B-cell line, WILL1, showing complex 8q24 translocation involving 14q32 and 6q27.

We established a novel mature B-cell line from a CD5 and CD10 double-positive diffuse large B-cell lymphoma patient, designated as WILL1. WILL1 cells were positive for CD5, CD10, CD19, and CD20. Spectral karyotype (SKY) analysis revealed chromosome 8 signals on 6q27 as well as 14q32.

Aggressive CD5-positive B-cell lymphoma after remission of CD5-negative follicular lymphoma with distinct immunoglobulin heavy chain rearrangement and translocation.

We report a unique, aggressive B-cell lymphoma that developed after the long-term remission of follicular lymphoma (FL). FL cells were negative for CD5, whereas aggressive lymphoma cells were positive for CD5. In FL, one immunoglobulin heavy chain gene (IGH) allele underwent V/D/J recombination and another t(14;18)(q32;q21).

Anti-tumor activity of an anti-endoglin monoclonal antibody is enhanced in immunocompetent mice.

In the present study, we investigated the mechanisms by which anti-endoglin (EDG; CD105) monoclonal antibodies (mAbs) suppress angiogenesis and tumor growth. Antihuman EDG mAb SN6j specifically bound to murine endothelial cells and was internalized into the cells in vitro. SN6j effectively suppressed angiogenesis in mice in the Matrigel plug assay.

Effective anti-angiogenic therapy of established tumors in mice by naked anti-human endoglin (CD105) antibody: differences in growth rate and therapeutic response between tumors growing at different sites.

We investigated anti-angiogenic/vascular targeting therapy of established tumors in immunocompetent mice using an anti-human endoglin (EDG; CD105) monoclonal antibody (mAb) SN6j. SN6j weakly cross-reacted with murine endothelial cells but reacted neither with colon-26 murine colon carcinoma cells nor with 4T1 murine mammary carcinoma cells. Systemic administration of naked (unconjugated) SN6j showed significant growth suppression of established tumors of colon-26 and 4T1 cells in immunocompetent BALB/c mice (P<0.

Activation of the endoplasmic reticulum stress pathway is associated with survival of myeloma cells.

The endoplasmic reticulum (ER) is an organelle in which proteins are modified. When unfolded proteins accumulate in the ER under various stresses, ER stress (ERS) pathways, including the induction of chaperones, are activated to protect the cell. However, when ERS is excessive, the cell undergoes apoptosis.

Dehydroxymethylepoxyquinomicin, a novel nuclear factor-kappaB inhibitor, induces apoptosis in multiple myeloma cells in an IkappaBalpha-independent manner.

Nuclear factor-kappaB (NF-kappaB) is constitutively activated in multiple myeloma cells. Several proteasome inhibitors have been shown to be effective against multiple myeloma and may act by inhibiting degradation of IkappaBalpha. Here, we examined the biological effects of a new type of NF-kappaB inhibitor, dehydroxymethylepoxyquinomicin (DHMEQ), which is reported to directly inhibit the cytoplasm-to-nucleus translocation of NF-kappaB.

Antiangiogenic chimeric anti-endoglin (CD105) antibody: pharmacokinetics and immunogenicity in nonhuman primates and effects of doxorubicin.

We generated a human/mouse chimeric antibody c-SN6j of human IgG1 isotype from a murine anti-human endoglin (EDG) monoclonal antibody (mAb) SN6j that suppressed angiogenesis, tumor growth and metastasis in mice. We determined pharmacokinetics (PKs) and immunogenicity of c-SN6j in monkeys after multiple i.v.

A nitric oxide synthase inhibitor, N(G)-nitro-l-arginine-methyl-ester, exerts potent antiangiogenic effects on plasmacytoma in a newly established multiple myeloma severe combined immunodeficient mouse model.

Angiogenesis is one of critical factors in sustaining the growth, invasion and metastasis of certain solid tumours and haematological malignancies such as multiple myeloma (MM). In the present study, we examined the anticancer potential of an inhibitor of nitric oxide synthase (NOS), NG-nitro-l-arginine methyl ester (L-NAME), in a novel severe combined immunodeficient mouse model (KHM mouse) that harbours the highly sanguineous plasmacytoma cell line KHM-4, derived from a patient with highly chemoresistant MM. KHM mice were intraperitoneally administered with either L-NAME, doxorubicin, melphalan, or paclitaxel.

Macrophage inflammatory protein-1 alpha is produced by human multiple myeloma (MM) cells and its expression correlates with bone lesions in patients with MM.

Macrophage inflammatory protein-1 alpha (MIP-1alpha) is a chemokine primarily associated with bone absorption. We examined whether MIP-1alpha was produced by purified fresh tumour cells isolated from bone marrow samples from 31 multiple myeloma (MM) patients. High levels of MIP-1alpha were found in supernatants of myeloma cell cultures.