Lipoid pneumonia with chronic myelomonocytic leukemia.

A case of lipoid pneumonia with chronic myelomonocytic leukemia is reported. A 61-year-old man was autopsied after suffering from myelodysplastic syndrome (chronic myelomonocytic leukemia) for 13 years. Interstitial lesions of the lungs were suspected as infiltration of leukemia cells before the autopsy.

The third-generation bisphosphonates inhibit proliferation of murine osteosarcoma cells with induction of apoptosis.

Third generation bisphosphonates (BPs), including YM175 and YM529, are known to inhibit bone resorption. The aim of this study was to evaluate the anti-tumor effects of these drugs on murine osteosarcoma cell lines, in terms of proliferation and apoptosis. We found that both YM175 and YM529 strongly inhibited the in vitro proliferation and induced apoptosis of murine osteosarcoma cells.

NS-187, a potent and selective dual Bcr-Abl/Lyn tyrosine kinase inhibitor, is a novel agent for imatinib-resistant leukemia.

Although the Abelson (Abl) tyrosine kinase inhibitor imatinib mesylate has improved the treatment of breakpoint cluster region-Abl (Bcr-Abl)-positive leukemia, resistance is often reported in patients with advanced-stage disease. Although several Src inhibitors are more effective than imatinib and simultaneously inhibit Lyn, whose overexpression is associated with imatinib resistance, these inhibitors are less specific than imatinib. We have identified a specific dual Abl-Lyn inhibitor, NS-187 (elsewhere described as CNS-9), which is 25 to 55 times more potent than imatinib in vitro.

Zoledronate synergises with imatinib mesylate to inhibit Ph primary leukaemic cell growth.

We examined the in vivo effects and safety of the third generation bisphosphonate, zoledronate (ZOL) alone and combined with imatinib mesylate against primary Philadelphia chromosome positive (Ph+) leukaemic cells. ZOL inhibited the prenylation of Rap1A in leukaemic cells in vitro and synergised with imatinib to enhance the survival of mice engrafted with cells from imatinib-responders, but not from non-responders because of mutated BCR-ABL. These findings suggest that the combination of ZOL and imatinib accelerate the eradication of Ph+ clone, resulting in better prognosis of Ph+ leukaemia patients who have not yet acquired mutations.

Zoledronic acid mediates Ras-independent growth inhibition of prostate cancer cells.

Zoledronic acid (ZOL), the most potent known bisphosphonate, is clinically efficacious against advanced prostate cancer, although the molecular mechanism by which bisphosphonates prevent prostate cancer cell growth remains unknown. Because Ras is the most thoroughly characterized member of the small G-proteins involved in the regulation of many cellular functions including several oncogenic pathways, the aim of this study was to clarify whether Ras is the molecular target of ZOL in prostate cancer cells. The prostate cancer cell lines PC-3, DU145, and LNCaP were used.

Intravesical administration of small interfering RNA targeting PLK-1 successfully prevents the growth of bladder cancer.

The mainstay in the management of invasive bladder cancer continues to be radical cystectomy. With regard to improvement of quality of life, however, therapies that preserve the bladder are desirable. We investigated the use of intravesical PLK-1 small interfering RNA (siRNA) against bladder cancer.

Cytotoxic effects of gammadelta T cells expanded ex vivo by a third generation bisphosphonate for cancer immunotherapy.

Nitrogen containing-bisphosphonates (N-BPs), widely used to treat bone diseases, have direct antitumor effects via the inactivation of Ras proteins. In addition to the direct antitumor activities, N-BPs expand gammadeltaT cells, which exhibit major histocompatibility complex-unrestricted lytic activity. BPs accumulate intermediate metabolites which may be tumor antigens in target cells.

The anti-leukemic efficacy of the third generation bisphosphonate ONO5920/YM529.

Ras proteins are frequently over-expressed in leukemia and contribute to leukemogenesis. We evaluated the anti-leukemic efficacy of a new third-generation bisphosphonate, ONO5920/YM529 (YM529). YM529 prevents the prenylation of Ras proteins and inhibited the growth of leukemic cells including a P-glycoprotein (P-gp) over-expressing cell line in a concentration- and time-dependent manner by inducing apoptosis in vitro.

A third-generation bisphosphonate, minodronic acid (YM529), augments the interferon alpha/beta-mediated inhibition of renal cell cancer cell growth both in vitro and in vivo.

Purpose: Minodronic acid (YM529) is a third-generation nitrogen-containing bisphosphonate. Here, we have investigated the therapeutic efficacy of YM529 against renal cell cancer (RCC) alone or in combination with IFN both in vitro and in vivo.

Experimental Design: One murine and eight human RCC cell lines were used for the in vitro studies and were subjected to a modified 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and Western blotting.

Rapid quantitation of immunoglobulin G antibodies specific for blood group antigens A and B by surface plasmon resonance.

Background: The measurement of immunoglobulin (Ig) G blood group A/B antibody(anti-A/B) levels is important for ABO-unmatched organ recipients because the effective removal of the antibodies improves their prognosis. Currently existing methods to detect IgG anti-A/B suffer limitations owing to high costs, low throughput, and poor adaptability to automation.

Study Design And Methods: We have developed a rapid means to quantitate IgG anti-A/B by surface plasmon resonance (SPR).

Monitoring luciferase-labeled cancer cell growth and metastasis in different in vivo models.

Cancer metastasis is infrequently evaluated in vivo, probably because of the few available models and the technical challenges associated with the detection of metastases. Here we show that the growth and metastases of HT1080 fibrosarcoma, A549 lung adenocarcinoma, and RENCA murine renal cancer cell lines in five different in vivo models can be successfully monitored by labeling the cells with luciferase prior to their implantation and then detecting their bioluminesence after injecting luciferin. We also used this in vivo imaging system to successfully demonstrate that YM529, a third generation bisphosphonate, inhibited the growth of sarcoma metastases in bone.

Efficacy of the third-generation bisphosphonate, zoledronic acid alone and combined with anti-cancer agents against small cell lung cancer cell lines.

Small cell lung cancer (SCLC) is one of the most aggressive types of cancers because of its early development of regional and distant metastases. Novel and more effective therapeutic strategies for the treatment of this disease are necessary. Bisphosphonates (BP), originally developed to treat bone disease, have recently been identified as attractive cancer theraptic agents.

Inhibition of leukemic cell growth by a novel anti-cancer drug (GUT-70) from calophyllum brasiliense that acts by induction of apoptosis.

During our search for cancer chemopreventing compounds derived from plant sources, we discovered that the natural product GUT-70, isolated from the stem bark of Calophyllum brasiliense collected in Brazil, significantly inhibits the growth of leukemic cells. GUT-70, characterized as a tricyclic coumarin, 5-methoxy-2,2-dimethyl-6-(2-methyl-1-oxo-2-butenyl) -10-propyl-2H,8H-benzo[1,2-b;3,4-b']dipyran-8-one (C(23)H(26)O(5)), inhibited all 6 human leukemic cell lines evaluated, including the P-glycoprotein overexpressing cell line, in a concentration and time-dependent manner with IC(50) values from 2-5 microM. Furthermore, GUT-70 did not inhibit colony formation by normal hematopoietic progenitors up to 30 microM and also did not inhibit the proliferation of normal human hepatocytes up to 30 microM.

Antiproliferative efficacy of the third-generation bisphosphonate, zoledronic acid, combined with other anticancer drugs in leukemic cell lines.

Bisphosphonates are widely used to treat bone diseases and appear to possess antitumor activity. Moreover, we recently found that a third-generation bisphosphonate, zoledronic acid (ZOL), synergistically interacts with imatinib in vitro and in vivo to induce antileukemic activity, and others have reported that ZOL interacts synergistically with paclitaxel. Thus, the efficacy of other antileukemic agents combined with ZOL should be evaluated experimentally.

p53-independent anti-tumor effects of the nitrogen-containing bisphosphonate zoledronic acid.

Zoledronic acid (ZOL), a nitrogen-containing bisphosphonate, exerts anti-tumor effects by inhibiting the prenylation of small GTPases. We have also reported that ZOL shows an anti-leukemic effect by inducing apoptosis throughout the S phase to the G(2) / M boundary. Here, we studied the effects of ZOL on various cell cycle regulators, including p53, cyclin-dependent kinases (CDKs), CDK inhibitors and cyclins, using BV173 leukemia and HCT116 colorectal carcinoma cell lines, harboring wild-type (wt-) p53.

MALT lymphoma at the base of the tongue developing without any background of immunodeficiency or autoimmune disease.

We report a very rare case of a mucosa-associated lymphoid tissue (MALT) lymphoma of the base of the tongue. A 61-year-old woman was admitted to our hospital for further examination of a 12 mm x 15 mm x 5 mm tongue tumor. Histological examination of the tumor revealed a marked lymphoepithelial lesion.

The third-generation bisphosphonate zoledronate synergistically augments the anti-Ph+ leukemia activity of imatinib mesylate.

Imatinib mesylate, a competitive inhibitor of Abl tyrosine kinase, is highly effective for the early stages of chronic myelogenous leukemia (CML), but remissions induced in advanced-phase CML and Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia tend to be relatively short-lived. Therefore, the search for agents that enhance the anti-Ph+ effect of imatinib mesylate is warranted. We investigated the combined effects of imatinib mesylate and the third-generation bisphosphonate zoledronate (ZOL) on Ph+ leukemias, because ZOL inhibited the prenylation of Ras-related proteins downstream of Bcr/Abl.