Effect of 6-aminonicotinamide on the pentose phosphate pathway:31P NMR and tumor growth delay studies

1996 ◽  
Vol 36 (6) ◽  
pp. 887-892 ◽  
Author(s):  
Jason A. Koutcher ◽  
Alan A. Alfieri ◽  
Cornelia Matei ◽  
Kristen L. Meyer ◽  
James C. Street ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Pentose Phosphate Pathway ◽  
31P Nmr ◽  
Pentose Phosphate ◽  
Growth Delay ◽  
Tumor Growth Delay

scholarly journals Effect of Dose, Timing and Delivery of Tumor Necrosis Factor Alpha as an Adjuvant in Cryosurgery of ELT-3 Uterine Leiomyoma (Fibroid) Tumor

2009 ◽  
Vol 3 (2) ◽  
Author(s):  
J. Jiang ◽  
J. Bischof
Keyword(s):  
Tumor Growth ◽  
Uterine Fibroid ◽  
Tumor Size ◽  
Uterine Leiomyoma ◽  
Mode Of Delivery ◽  
Growth Delay ◽  
Tumor Growth Delay ◽  
Tnf Α ◽  
Pre Treatment

Uterine leiomyoma (fibroid or myoma) is the most common indication for hysterectomy in premenopausal women. Cryomyolysis is a uterus sparing procedure in which a myoma is frozen by a cryoprobe, thereby causing tissue necrosis upon thawing and eventual reduction in myoma size. Unfortunately, although the iceball is readily visualized (by ultrasound-US or magnetic resonance-MR), the tissue at the periphery of the iceball is not completely destroyed. One potential solution to this problem is the use of cryosurgical adjuvants that increase cryosurgical image guidance and efficacy. Previous work in our lab has shown that TNF-α (native or as the nanodrug, CYT-6091, Cytimmune Sciences, Inc.) can act synergistically with cryosurgery to destroy all prostate cancer within an iceball. Building on this work, the current study was designed to test TNF-α as an adjuvant in an in vivo model of uterine fibroid (ELT-3) in a nude mouse. The aims of this study are to characterize in vivo: 1) the destruction of the uterine fibroid over time after cryosurgery; 2) the effect of TNF-α pre-treatment on enhancement of cryosurgery; 3) the effect of TNF-α dose, pre-treatment time and mode of delivery on the above and to note any toxicities. ELT–3 rat uterine fibroid cells were grown in the hind limb of female nude mice. TNF-α at various dose (2μg and 5μg) was administered at 1, 2 and 4 hours before cryotreatment in native or CYT-6091. Native TNF-α was injected either intra-tumorally or peri-tumorally. Injecting TNF-α solution into the center of the tumor comprised the intra-tumoral approach. For peri-tumoral injection, TNF-α solution was injected at each one of eight evenly distributed points spanning the circumference of the tumor base. CYT-6091 was administered by i.v. injection only. Cryosurgery was performed with a modified 1 mm diameter cryoprobe tip (−120°C). Freezing was allowed to continue to the visible edge of the tumor. Injury was assessed by measuring tumor-growth delay. Baseline tumor size was measured on day 0; fold-changes in tumor size are reported relative to size at day 0. Toxicity was evaluated by survival rate. Groups were 4–6 animals in each group. The data suggests that pre-treatment with TNF-α before cryosurgery significantly enhances visually guided destruction of uterine leiomyoma, and that the dose, timing and mode of delivery are important variables in optimization of this combination treatment. First, it was observed that at least four hours pretreatment with TNF-α is required to obtain the synergistic effect of TNF-α and cryoinjury. Second, peri-tumoral injection of native TNF-α, was the most effective delivery method to enhance cryoinjury at low dose (2μg), however it was also the most toxic method at high dose (5μg). On the other hand, CYT-6091, although less effective than peri-tumoral injection at 2μg, was the safest delivery mode (0% lethality at 2μg; 33% at 5μg). Finally, CYT-6091 delivery at 5μg with cryosurgery resulted in a dramatic tumor growth delay compared with cryosurgery alone. Therefore, i.v. injection of CYT-6091 followed by cryosurgery allowed the highest dose of TNF-α, the least toxicity and the best overall myoma reduction. Funding: R01 CA075284, American Medical Systems, Inc. TNF-α and CYT-6091: Cytimmune Sciences, Inc.

Inhibition of Poly(ADP-Ribose) Polymerase Enhances Cell Death and Improves Tumor Growth Delay in Irradiated Lung Cancer Models

2007 ◽  
Vol 13 (10) ◽  
pp. 3033-3042 ◽  
Author(s):  
Jeffrey M. Albert ◽  
Carolyn Cao ◽  
Kwang Woon Kim ◽  
Christopher D. Willey ◽  
Ling Geng ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Death ◽  
Tumor Growth ◽  
Growth Delay ◽  
Tumor Growth Delay ◽  
Cancer Models

TRU-016, An Anti-CD37 SMIP™ Biologic, In Combination with Other Therapeutic Drugs In Models of Non-Hodgkin's Lymphoma

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3931-3931 ◽  
Author(s):  
Paul A. Algate ◽  
Jennifer Wiens ◽  
Christy Nilsson ◽  
Mien Sho ◽  
Debra T. Chao ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Follicular Lymphoma ◽  
B Cell ◽  
Cell Lymphoma ◽  
Combination Index ◽  
Growth Delay ◽  
Tumor Growth Delay ◽  
B Cell Malignancies

Abstract Abstract 3931 Background: CD37 is a 50–55 kDa heavily glycosylated member of the tetraspanin superfamily of molecules. This cell surface protein is expressed on normal and transformed B-cells, and has been implicated in diverse processes including cellular activation and proliferation, cell motility, and cell-cell adhesion. TRU-016 is a novel humanized anti-CD37 SMIP™ protein. Pre-clinical studies have demonstrated that anti-CD37 SMIP™ protein mediates caspase-independent direct killing of normal and malignant B-cells, a mechanism of action that appears to be different than CD20 therapies. In addition, TRU-016 results in indirect killing through NK cell mediated SMIP-protein directed cellular cytotoxicity (SDCC). The therapeutic potential of TRU-016 against several subsets of B-cell malignancies is currently being investigated in the clinic. Methods: The ability of TRU-016 to interact and increase cell killing with established therapeutics rituximab (anti-CD20 antibody), bendamustine (bi-functional alkylating agent/nucleoside analog), LY294002 (PI3K inhibitor) and temsirolimus (mTOR inhibitor) was investigated in vitro using the Rec-1 (mantle cell lymphoma) and SU-DHL-6 (diffuse large B cell lymphoma) cell lines. Individual drugs were tested in combination with TRU-016 as well as in a multiple drug cocktail. Combination index analyses were performed for drug combinations over the 20–90% effect levels. To determine whether in vitro synergy could be recapitulated in vivo, DoHH-2 (follicular lymphoma) xenografts were treated with TRU-016, bendamustine, and the combination of TRU-016 and bendamustine with or without rituximab. Furthermore, the effect of the dosing schedule with the combination of TRU-016 and rituximab was explored by comparing the treatment over a short time period to an extended (maintenance) dosing regimen. CD37 expression on the tumor xenografts was evaluated post different treatment by immunohistochemistry. Results: Combination index analyses determined that the killing effects of TRU-016 was synergistic with rituximab, bendamustine and temsirolimus in NHL models. Furthermore, TRU-016 provided additional efficacy when added to the combination of rituximab and bendamustine. In vivo results demonstrated that the in vitro synergy results were applicable to a more complex in vivo disease model. The combination of TRU-016 with bendamustine or rituximab resulted in increased tumor growth delay compared to that attained with the individual drugs. The addition of TRU-016 to the combination of bendamustine and rituximab resulted in increased tumor growth delay compared to the two drugs alone. The observed efficacy of the combination of TRU-016 and rituximab could be extended with repeated (maintenance) dosing with tumor free survival being observed beyond the 35 days of dosing. The combination of TRU-016 with temsirolimus also resulted in a reduction of tumor growth compared to either molecule alone. CD37 target expression was detected in the xenograft tumors post-treatment with all drugs tested. Conclusions: TRU-016 in combination with rituximab, bendamustine or temsirolimus increased cell killing of NHL cells in vitro over that observed for each agent alone. Furthermore, the triple combination of TRU-016 with rituximab, bendamustine or temsirolimus displayed greater anti-tumor activity in vivo than each of the agents alone against a follicular lymphoma tumor model. The addition of TRU-016 to a combination of rituximab and bendamustine resulted in increased killing in vitro and in vivo. The combinatorial activity of TRU-016 and rituximab in vivo was increased when the drugs were administered over a longer period. These results provide preclinical rationale for the potential different combinations of TRU-016 with several established therapeutics for the treatment of NHL and related B-cell malignancies. Disclosures: Algate: Trubion Pharmaceuticals: Employment. Wiens:Trubion Pharmaceuticals: Employment. Nilsson:Trubion Pharmaceuticals: Employment. Sho:Facet/Abbott: Employment. Chao:Facet/Abbott: Employment. Starling:Facet/Abbott: Employment. Gordon:Trubion Pharmaceuticals: Employment.

An engineered immunotherapy (NKTR-214) with altered selectivity toward the IL2 receptor: Efficacy and tolerability in a murine tumor model.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 3060-3060
Author(s):  
Deborah H. Charych ◽  
Murali Addepalli ◽  
Steve Lee ◽  
Thomas Chang ◽  
Xiaofeng Liu ◽  
...  
Keyword(s):  
T Cells ◽  
Tumor Growth ◽  
Immune Cells ◽  
Tumor Model ◽  
Optimal Dose ◽  
Growth Delay ◽  
Blue Dye ◽  
Tumor Localization ◽  
Tumor Growth Delay ◽  
Polymer Conjugation

3060 Background: Cytokine-based immunotherapy has been successful for the treatment of cancer, with potential for durable responses in multiple indications. One approach towards stimulating the immune system is to target the heterotrimeric interleukin2 receptor, IL2R. NKTR-214 uses polymer technology to alter receptor subunit selectivity to favor expansion of CD8+ memory effector T cells (CD8T) in the tumor over CD4+ regulatory T cells (Treg). In addition, polymer conjugation is designed to improve exposure and enhance tumor localization, significantly improving efficacy, modulating vascular leak syndrome (VLS) and allowing flexible dosing regimens. Methods: C57BL/6 mice bearing established subcutaneous B16F10 melanoma were treated with NKTR-214 at a variety of doses (0.25-4.0 mg/kg) and schedules (q5dx3 to q14dx2). Mice treated with clinically validated IL2 were administered 3mg/kg, bidx5 for 2 cycles. Efficacy was measured by monitoring tumor volumes. Tolerability was evaluated by survival. VLS was measured by injection of Evans Blue dye followed by colorimetry in lungs. Tumor immunotyping, by flow cytometry. Results: Tumors from mice receiving NKTR-214 had a CD8/Treg ratio of over 1,000 versus 14 for IL2. NKTR-214 administered at 2 mg/kg, q9dx3 was identified as the optimal regimen and showed tumor growth delay of 26 days compared to 9 days for optimally dosed IL2. 90% of NKTR-214 treated mice tolerated treatment compared to 67% for IL2. VLS was completely resolved prior to administration of the next dose of NKTR-214, unlike IL2. NKTR-214 was well tolerated in rats at two schedules, at MTD. Conclusions: NKTR-214 is a highly differentiated cytokine with a new mechanism of action that may provide options for cancer immunotherapy. Polymer conjugation of a clinically validated cytokine alters the IL2R selectivity to favor expansion of tumor killing immune cells (CD8T) over regulatory immune cells (Treg) in the tumor. The conjugate is also designed to improve exposure and enhance tumor localization, offering more options of dose and schedule. The optimal dose and schedule is cytokine-sparing, provides substantial tumor growth delay, and reduces toxicity.

OC-0153 EGFR-INHIBITION AND RADIOTHERAPY IN HEAD AND NECK CANCER XENOGRAFTS: HYPOXIA, PROLIFERATION AND TUMOR GROWTH DELAY

2012 ◽  
Vol 103 ◽  
pp. S59
Author(s):  
H. Stegeman ◽  
J.H.A.M. Kaanders ◽  
A.J. van der Kogel ◽  
M. Iida ◽  
D.L. Wheeler ◽  
...  
Keyword(s):  
Head And Neck Cancer ◽  
Tumor Growth ◽  
Head And Neck ◽  
Neck Cancer ◽  
Growth Delay ◽  
Tumor Growth Delay ◽  
Egfr Inhibition

scholarly journals Cordycepin-enriched Cordyceps militaris induces immunomodulation and tumor growth delay in mouse-derived breast cancer

2013 ◽  
Vol 30 (4) ◽  
pp. 1996-2002 ◽  
Author(s):  
MIN-HO JEONG ◽  
CHANG-MIN LEE ◽  
SANG-WHA LEE ◽  
SU-YEONG SEO ◽  
MIN-JEONG SEO ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Growth ◽  
Cordyceps Militaris ◽  
Growth Delay ◽  
Tumor Growth Delay

61 EFFECTS OF EGFR-INHIBITION AND RADIOTHERAPY ON HYPOXIA, PROLIFERATION AND TUMOR GROWTH DELAY IN HUMAN TUMOR XENOGRAFTS

2012 ◽  
Vol 102 ◽  
pp. S21
Author(s):  
H. Stegeman ◽  
P. Span ◽  
A.J. van der Kogel ◽  
D. Wheeler ◽  
J. Kaanders ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Human Tumor ◽  
Growth Delay ◽  
Tumor Growth Delay ◽  
Human Tumor Xenografts ◽  
Tumor Xenografts ◽  
Egfr Inhibition

scholarly journals PRIMA-1Met/APR-246 Induces Apoptosis and Tumor Growth Delay in Small Cell Lung Cancer Expressing Mutant p53

2011 ◽  
Vol 17 (9) ◽  
pp. 2830-2841 ◽  
Author(s):  
Roza Zandi ◽  
Galina Selivanova ◽  
Camilla Laulund Christensen ◽  
Thomas Alexander Gerds ◽  
Berthe Marie Willumsen ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Tumor Growth ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Growth Delay ◽  
Mutant P53 ◽  
Small Cell Lung ◽  
Tumor Growth Delay
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