Feasibility of using the drug-induced apoptosis assay (MiCK assay) in mesothelioma as compared to non-small cell lung cancer (NSCLC).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e18538-e18538
Author(s):  
Dennis A. Wigle ◽  
Allan Hallquist ◽  
Cary Presant ◽  
Julian R. Molina
Keyword(s):  
Ovarian Cancer ◽  
Controlled Trial ◽  
Acute Myelocytic Leukemia ◽  
Significant Activity ◽  
Drug Induced ◽  
Myelocytic Leukemia ◽  
Apoptosis Assay ◽  
Induced Apoptosis ◽  
Clinical Trial Information

e18538 Background: The drug-induced apoptosis MiCK assay has been predictive of outcomes in acute myelocytic leukemia, ovarian cancer, and a variety of solid tumors including breast cancer (Cancer Research 2012; 72:3901). We compared MiCK assay results in mesothelioma patients (pts) with NSCLC pts. Methods: Specimens from tissue or effusions were submitted to a central lab, processed to purify neoplastic cells, and a MiCK assay was performed as described (Cancer 2012; 118: 4877). Best chemotherapy regimens are defined as drugs/combinations with highest kinetic units (KU) of apoptosis +/- 1 SD compared to other drugs (this definition was predictive of outcomes in ovarian cancer). Active drugs have results over 1.0 KU of apoptosis. Results: 10 specimens have been submitted and 7 have been successful. Mean age was 69 and mean number of prior lines of therapy were 0.7 in 3 mesothelioma pts and 2.0 in 4 NSCLC pts. Mean number of drugs or combinations assayed successfully were 41 in mesothelioma and 20 in NSCLC. In mesothelioma, best active chemotherapy regimens (>1.0 KU) have been pemetrexed+doxorubicin, epirubicin, idarubicin, cyclophosphamide, ifosfamide, and dactinomycin. In NSCLC, best active regimens have been doxorubicin+cisplatin, irinotecan, and cyclophosphamide+doxorubicin+vincristine. In mesothelioma pts, the assay has been able to identify unexpected significant activity of several drugs: epirubicin, idarubicin, daunorubicin, dactinomycin, bendamustine, melphalan, vincristine, topotecan, azacytidine and bortezomib. Conclusions: Use of the MiCK assay in mesothelioma is at least as successful in the laboratory as it is in NSCLC. Unexpected new leads for innovative therapeutic strategies have been identified by the in vitro results. This feasibility study justifies a prospective controlled trial of the MiCK assay in mesothelioma and NSCLC pts. Clinical trials of drugs with unexpected activity are warranted in mesothelioma pts. Clinical trial information: NCT 01770665.

Correlation of the microculture-kinetic drug-induced apoptosis assay with patient outcomes in initial treatment of adult acute myelocytic leukemia

2012 ◽  
Vol 54 (3) ◽  
pp. 528-534 ◽  
Author(s):  
Stephen A. Strickland ◽  
Anastasios Raptis ◽  
Allan Hallquist ◽  
James Rutledge ◽  
Michael Chernick ◽  
...  
Keyword(s):  
Patient Outcomes ◽  
Initial Treatment ◽  
Acute Myelocytic Leukemia ◽  
Drug Induced ◽  
Myelocytic Leukemia ◽  
Apoptosis Assay ◽  
Induced Apoptosis

scholarly journals Enhanced expression of the granulocyte-macrophage colony stimulating factor gene in acute myelocytic leukemia cells following in vitro blast cell enrichment

Blood ◽  
1988 ◽  
Vol 72 (4) ◽  
pp. 1329-1332 ◽  
Author(s):  
DC Kaufman ◽  
MR Baer ◽  
XZ Gao ◽  
ZQ Wang ◽  
HD Preisler
Keyword(s):  
T Cell ◽  
Leukemic Cells ◽  
Acute Myelocytic Leukemia ◽  
Colony Stimulating Factor ◽  
Gm Csf ◽  
Myelocytic Leukemia ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

Expression of the granulocyte-macrophage colony-stimulating factor (GM- CSF) gene in acute myelocytic leukemia (AML) was assayed by Northern blot analysis. GM-CSF messenger RNA (mRNA) was detected in the freshly obtained mononuclear cells of only one of 48 cases of AML, in contrast with recent reports that GM-CSF mRNA might be detected in half of the cases of AML when RNA is prepared from T-cell- and monocyte-depleted leukemic cells. We did find, however, that expression of the GM-CSF gene was detectable in five of ten cases after in vitro T-cell and monocyte depletion steps. Additional studies suggest that expression of GM-CSF in the bone marrow of the one positive case, rather than being autonomous, was under exogenous control, possibly by a paracrine factor secreted by marrow stromal cells. These studies emphasize the potential for altering in vivo patterns of gene expression by in vitro cell manipulation.

scholarly journals VENO-OCCLUSIVE DISEASE (VOD): A NEWLY RECOGNIZED FORM OF DRUG-INDUCED LIVER DISEASE IN ACUTE MYELOCYTIC LEUKEMIA (AML)

1977 ◽  
Vol 11 (4) ◽  
pp. 478-478
Author(s):  
J Lawrence Naiman ◽  
Robert S Wimmer ◽  
Dale S Huff ◽  
H Theodore Harcke
Keyword(s):  
Liver Disease ◽  
Occlusive Disease ◽  
Acute Myelocytic Leukemia ◽  
Drug Induced ◽  
Myelocytic Leukemia

Phase I and pharmacologic study of paclitaxel administered weekly in patients with relapsed ovarian cancer.

1997 ◽  
Vol 15 (1) ◽  
pp. 187-192 ◽  
Author(s):  
D Fennelly ◽  
C Aghajanian ◽  
F Shapiro ◽  
C O'Flaherty ◽  
M McKenzie ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Phase I ◽  
Standard Dose ◽  
Advanced Ovarian Cancer ◽  
Dose Intensity ◽  
Maximum Tolerated Dose ◽  
Significant Activity ◽  
Weekly Schedule ◽  
The Mean

PURPOSE Paclitaxel has shown significant activity in advanced ovarian cancer. In vitro studies with paclitaxel have suggested that fractionated brief infusion schedules may be more effective than the standard 24-hour infusion. We commenced a phase I evaluation of escalating-dose paclitaxel (40, 50, 60, 80, 100 mg/m2) administered weekly as a 1-hour infusion in patients with recurrent ovarian cancer. All patients had received prior paclitaxel and cisplatin therapy. All patients received standard premedication. PATIENTS AND METHODS Eighteen patients are assessable on this phase I study. The mean age was 54 years (range, 48 to 74). The median number of prior chemotherapy regimens was three (range, two to five). The mean paclitaxel-free interval was 10.1 months (range, 1 to 24). RESULTS A total of 194 cycles of therapy were administered, with a mean of 10 (range, one to 12) per patient. No mucositis or grade III neuropathy was seen. Alopecia occurred in one out of 18 assessable patients. The mean neutrophil nadir was 4.0 x 10(9)/L. At the top dose level (100 mg/m2) delivered, dose-intensity was 90.75% of that planned and greater than two fold the standard dose-intensity. Partial responses were seen in four of 13 assessable patients (30%). Two patients with progression of disease on standard three-week paclitaxel schedules switched to a weekly schedule with demonstrated response. Increasing paclitaxel dose correlated with measured area under the curve (AUC) (R2 = .614). Dose-limiting toxicity was reached at 100 mg/m2 with two of three patients experiencing a treatment delay, thus defining a maximum-tolerated dose of 80 mg/m2 in this group of heavily pretreated patients on this weekly schedule. CONCLUSION (1) Paclitaxel administered as a 1-hour infusion is well tolerated; (2) this schedule of administration does not result in cumulative myelosuppression; and (3) this schedule of administration results in dose-intensive paclitaxel delivery with a favorable toxicity profile.

Multidrug-resistance phenotype and clinical responses to gemtuzumab ozogamicin

Blood ◽  
2001 ◽  
Vol 98 (4) ◽  
pp. 988-994 ◽  
Author(s):  
Michael L. Linenberger ◽  
Tom Hong ◽  
David Flowers ◽  
Eric L. Sievers ◽  
Ted A. Gooley ◽  
...  
Keyword(s):  
Multidrug Resistance ◽  
Annexin V ◽  
Poor Response ◽  
Surface Expression ◽  
Gemtuzumab Ozogamicin ◽  
Drug Induced ◽  
Reversal Agents ◽  
Clinical Resistance ◽  
Induced Apoptosis

Expression of multidrug resistance (MDR) features by acute myeloid leukemia (AML) cells predicts a poor response to many treatments. The MDR phenotype often correlates with expression of P-glycoprotein (Pgp), and Pgp antagonists such as cyclosporine (CSA) have been used as chemosensitizing agents in AML. Gemtuzumab ozogamicin, an immunoconjugate of an anti-CD33 antibody linked to calicheamicin, is effective monotherapy for CD33+ relapsed AML. However, the contribution of Pgp to gemtuzumab ozogamicin resistance is poorly defined. In this study, blast cell samples from relapsed AML patients eligible for gemtuzumab ozogamicin clinical trials were assayed for Pgp surface expression and Pgp function using a dye efflux assay. In most cases, surface expression of Pgp correlated with Pgp function, as indicated by elevated dye efflux that was inhibited by CSA. Among samples from patients who either failed to clear marrow blasts or failed to achieve remission, 72% or 52%, respectively, exhibited CSA-sensitive dye efflux compared with 29% (P = .003) or 24% (P < .001) among samples from responders. In vitro gemtuzumab ozogamicin–induced apoptosis was also evaluated using an annexin V–based assay. Low levels of drug-induced apoptosis were associated with CSA-sensitive dye efflux, whereas higher levels correlated strongly with achievement of remission and marrow blast clearance. In vitro drug-induced apoptosis could be increased by CSA in 14 (29%) of 49 samples exhibiting low apoptosis in the absence of CSA. Together, these findings indicate that Pgp plays a role in clinical resistance to gemtuzumab ozogamicin and suggest that treatment trials combining gemtuzumab ozogamicin with MDR reversal agents are warranted.

scholarly journals Demethoxycurcumin inhibited human epithelia ovarian cancer cells’ growth via up-regulating miR-551a

Tumor Biology ◽  
2017 ◽  
Vol 39 (3) ◽  
pp. 101042831769430 ◽  
Author(s):  
Zhenhua Du ◽  
Xianqun Sha
Keyword(s):  
Ovarian Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Ovarian Cancer Cells ◽  
Natural Form ◽  
Ovarian Cancer Cell Lines ◽  
Induced Apoptosis ◽  
Tumor Suppressive Function ◽  
Cancer Tissues

Curcumin is a natural agent that has ability to dampen tumor cells’ growth. However, the natural form of curcumin is prone to degrade and unstable in vitro. Here, we demonstrated that demethoxycurcumin (a curcumin-related demethoxy compound) could inhibit cell proliferation and induce apoptosis of ovarian cancer cells. Moreover, IRS2/PI3K/Akt axis was inactivated in cells treated with demethoxycurcumin. Quantitative real-time reverse transcription polymerase chain reaction demonstrated that miR-551a was down-regulated in ovarian cancer tissues and ovarian cancer cell lines. Over-expression of miR-551a inhibited cell proliferation and induced apoptosis of ovarian cancer cells, whereas down-regulation of miR-551a exerted the opposite function. Luciferase assays confirmed that there was a binding site of miR-551a in IRS2, and we found that miR-551a exerted tumor-suppressive function by targeting IRS2 in ovarian cancer cells. Remarkably, miR-551a was up-regulated in the cells treated with demethoxycurcumin, and demethoxycurcumin suppressed IRS2 by restoration of miR-551a. In conclusion, demethoxycurcumin hindered ovarian cancer cells’ malignant progress via up-regulating miR-551a.

scholarly journals A designed peptide targeting CXCR4 displays anti-acute myelocytic leukemia activity in vitro and in vivo

2014 ◽  
Vol 4 (1) ◽  
Author(s):  
Xiaojin Li ◽  
Hua Guo ◽  
Yanlian Yang ◽  
Jie Meng ◽  
Jian Liu ◽  
...  
Keyword(s):  
Acute Myelocytic Leukemia ◽  
Myelocytic Leukemia ◽  
Peptide Targeting

Karnofsky Memorial Lecture. Breaking the cure barrier.

1983 ◽  
Vol 1 (2) ◽  
pp. 75-90 ◽  
Author(s):  
J F Holland
Keyword(s):  
Breast Cancer ◽  
Ovarian Cancer ◽  
Young Adults ◽  
Adjuvant Chemotherapy ◽  
Cancer Therapy ◽  
Pure Form ◽  
Memorial Lecture ◽  
Acute Myelocytic Leukemia ◽  
Conceptual Problem ◽  
Myelocytic Leukemia

Breaking the cure barrier is a biologic and a conceptual problem that has already been accomplished for several tumors. It is helpful to consider neoplasms in mathematical terms as many-celled tumors (polycytomas: kilocytomas, megacytomas, gigacytomas, and teracytomas). A new chemotherapeutic taxonomy recognizes curable, subcurable, and precurable cancers each with definable characteristics. A simplified technique of recognizing early cures is described by calculating the probability that an interruption in an exponential failure slope occurred by chance. Examples of cures of acute myelocytic leukemia, of superior chemotherapy for Hodgkin's disease in young adults, and of superior adjuvant chemotherapy for breast cancer are given. The interaction of surgery with chemotherapy is illustrated in pure form in acute myelocytic leukemia and in ovarian cancer. Curative chemotherapy is closer at hand than is generally believed. Nomograms for cure prediction are presented as inducements to contemplate curative approaches to cancer therapy.

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