scholarly journals Effect of shock waves combined with cytostatics on the growths of tumors in vivo

2019 ◽  
pp. S475-S481
Author(s):  
J. Zeman ◽  
J. Benes ◽  
P. Pouckova ◽  
M. Zadinova ◽  
P. Lukes
Keyword(s):  
Shock Wave ◽  
Shock Waves ◽  
Tumor Cells ◽  
Treated Group ◽  
Tumor Growth Inhibition ◽  
Physical Parameters ◽  
Composite Anode ◽  
The Right ◽  
Entire Apparatus

Based on their field of application, the physical parameters of shock waves differ. Experiments referred to in this article used tandem shock waves generated on the surface of a composite anode. There, individual pores of the anode produce multichannel discharges. The composite anode may have a variety of shapes, which, consequently, influence the arrangement of the entire apparatus and the area of their application. Experiments referred to in this article utilise an anode divided into two parts that generated tandem shock waves. The previously conducted experiments have clearly shown that the effect of a tandem shock wave can be very well localized in the focal area, causing necrosis and apoptosis of the tumor cells, and enhancing the effect of cytostatics. This study investigated the effect of tandem shock waves with concomitantly administered cytostatics. We conducted our experiments on Lewis rats. The rats were injected with syngeneic sarcoma tumor cells intradermally and caudally on both the right and left sides. The highest rate of tumor growth inhibition was observed in the cisplatin-treated group that was subsequently treated with shock waves. The effect of shock waves on cell membranes is well described as they increase their permeability due to sonodynamic effect induced by cavitation. The results of experiments referred to in this article conducted in vivo in experimental animals enable us to note that the shock wave increases the effect of chemotherapy administered.

The In Vitro and In Vivo Effects of Extracorporeal Shock Waves on Tumor Cells

1988 ◽  
pp. 351-355
Author(s):  
Gerhard J. Fuchs ◽  
Randall F. Randazzo ◽  
Anna M. Fuchs ◽  
Arnulf Stenzl ◽  
Christian G. Chaussy
Keyword(s):  
Shock Waves ◽  
Tumor Cells ◽  
Extracorporeal Shock Waves ◽  
In Vivo Effects

scholarly journals Highly Differentiated Anti-CD47 Antibody, AO-176, Potently Inhibits Hematologic Malignancies Alone and in Combination

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 1844-1844
Author(s):  
John Richards ◽  
Myriam N Bouchlaka ◽  
Robyn J Puro ◽  
Ben J Capoccia ◽  
Ronald R Hiebsch ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Combination Therapy ◽  
Tumor Growth ◽  
Growth Inhibition ◽  
Tumor Cells ◽  
Tumor Growth Inhibition ◽  
Employment Equity ◽  
Equity Ownership

AO-176 is a highly differentiated, humanized anti-CD47 IgG2 antibody that is unique among agents in this class of checkpoint inhibitors. AO-176 works by blocking the "don't eat me" signal, the standard mechanism of anti-CD47 antibodies, but also by directly killing tumor cells. Importantly, AO-176 binds preferentially to tumor cells, compared to normal cells, and binds even more potently to tumors in their acidic microenvironment (low pH). Hematological neoplasms are the fourth most frequently diagnosed cancers in both men and women and account for approximately 10% of all cancers. Here we describe AO-176, a highly differentiated anti-CD47 antibody that potently targets hematologic cancers in vitro and in vivo. As a single agent, AO-176 not only promotes phagocytosis (15-45%, EC50 = 0.33-4.1 µg/ml) of hematologic tumor cell lines (acute myeloid leukemia, non-Hodgkin's lymphoma, multiple myeloma, and T cell leukemia) but also directly targets and kills tumor cells (18-46% Annexin V positivity, EC50 = 0.63-10 µg/ml) in a non-ADCC manner. In combination with agents targeting CD20 (rituximab) or CD38 (daratumumab), AO-176 mediates enhanced phagocytosis of lymphoma and multiple myeloma cell lines, respectively. In vivo, AO-176 mediates potent monotherapy tumor growth inhibition of hematologic tumors including Raji B cell lymphoma and RPMI-8226 multiple myeloma xenograft models in a dose-dependent manner. Concomitant with tumor growth inhibition, immune cell infiltrates were observed with elevated numbers of macrophage and dendritic cells, along with increased pro-inflammatory cytokine levels in AO-176 treated animals. When combined with bortezomib, AO-176 was able to elicit complete tumor regression (100% CR in 10/10 animals treated with either 10 or 25 mg/kg AO-176 + 1 mg/kg bortezomib) with no detectable tumor out to 100 days at study termination. Overall survival was also greatly improved following combination therapy compared to animals treated with bortezomib or AO-176 alone. These data show that AO-176 exhibits promising monotherapy and combination therapy activity, both in vitro and in vivo, against hematologic cancers. These findings also add to the previously reported anti-tumor efficacy exhibited by AO-176 in solid tumor xenografts representing ovarian, gastric and breast cancer. With AO-176's highly differentiated MOA and binding characteristics, it may have the potential to improve upon the safety and efficacy profiles relative to other agents in this class. AO-176 is currently being evaluated in a Phase 1 clinical trial (NCT03834948) for the treatment of patients with select solid tumors. Disclosures Richards: Arch Oncology Inc.: Employment, Equity Ownership, Other: Salary. Bouchlaka:Arch Oncology Inc.: Consultancy, Equity Ownership. Puro:Arch Oncology Inc.: Employment, Equity Ownership. Capoccia:Arch Oncology Inc.: Employment, Equity Ownership. Hiebsch:Arch Oncology Inc.: Employment, Equity Ownership. Donio:Arch Oncology Inc.: Employment, Equity Ownership. Wilson:Arch Oncology Inc.: Employment, Equity Ownership. Chakraborty:Arch Oncology Inc.: Employment, Equity Ownership. Sung:Arch Oncology Inc.: Employment, Equity Ownership. Pereira:Arch Oncology Inc.: Employment, Equity Ownership.

The Effects of Berbamine in Nude Mice Xenograft Model of Human Leukemic Cells.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4413-4413
Author(s):  
Dong Wu ◽  
Maofang Lin
Keyword(s):  
Side Effects ◽  
Tumor Cells ◽  
Nude Mice ◽  
Chinese Herb ◽  
Leukemic Cell ◽  
Treated Group ◽  
Leukemic Cells ◽  
Tumor Weight ◽  
Group A

Abstract Background: Berbamine is a kind of bis-benzylisoquinoline extracted from Chinese herb. In our past research, it had been proven that berbamine could obviously inhibit the proliferation and induce apoptosis in different kinds of leukemic cell lines including K562, Jurkat, NB4 in a time-and dosage-dependent manner in vitro. The down-regulation expressions of survivin gene, bcr/abl gene and bcr/abl -related P210 may play an important role in the apoptotic effect of Berbamine in leukemic cells. However, the effects in vivo and its mechanism remain to be identified. In this study, the effects of berbamine in nude mice bearing human leukemic cell xenografts were tested. Methods: The nude mice (BALB/C-nu/nu) were pre-treated with X ray 400cGy/2min, then 2×107 K562 cells and Jurkat cells were subcutaneously injected into the mice respectively. Rapid growth of solid tumors was observed in nude mice. One week later, the tumor-bearing mice were randomly divided into three treatment groups: untreated controls; berbamine-treated group (a dose of 1.0mg/day × 20 day, subcutaneously injected); Ara-C-treated group(a dose of 0.8mg/day, × 7 day, subcutaneously injected). Four weeks later, all the experimental mice were euthanized. Results: Mice that received berbamine had significantly slower tumor growth rate than did untreated mice. In K562-bearing mice, the tumor weight of berbamine-treated group was lower than that of the control group(1.46g±0.43g vs 2.90g±0.94g, P<0.01 )and the inhibition rate was 49.66%. In Jurkat-bearing mice, the tumor weight of berbamine-treated group was also lower than that of untreated group(0.96g±0.64g vs 2.28g±0.33g, P<0.01), although it was comparable to that of Ara-C-treated group(0.54g±0.38g, P=0.311). The inhibition rates were 57.89% and 76.32% respectively. Moreover, in Jurkat-bearing mice berbamine inhibited the tumor cells invasion into bone marrow. In K562-bearing mice, berbamine down-regulated the expression level of bcr/abl gene of tumor cells ((berbamine-treated group 1.07±0.05 vs untreated group 1.58±0.24, P<0.05). In addition, no harmful side effects were attributed to berbamine. Conclusion: In vivo, berbamine could aslo take a better antileukemia effect and the dose of berbamine used was safe with almost no side effects in nude mice. Berbamine extracted from Chinese herb might be a promising candidate of new drugs for clinical anticancer treatment, especially for bcr-abl+ diseases.

Prolonged Coumadin Treatment as an Adjuvant to Surgery in an Experimental Colon Carcinoma

1970 ◽  
Vol 56 (3) ◽  
pp. 165-173 ◽  
Author(s):  
Domenico Agostino
Keyword(s):  
Prothrombin Time ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Colon Carcinoma ◽  
Hepatic Metastases ◽  
Treated Group ◽  
Surgical Wound ◽  
Severe Hemorrhage

The effect of prolonged Coumadin treatment of tumor cells and metastases was studied using an experimental colon carcinoma of the rat. In vivo Coumadin induced significant changes in the number of circulating tumor cells and in the formation of hepatic metastases. These metastases were reduced from 31 % of the control animals to 15% of the Coumadin treated group. Prothrombin time, although prolonged to approximately double control values, did not cause severe hemorrhage. No deaths were reported in the anticoagulated animals, although some oozing from the surgical wound was detected. This oozing subsided following termination of treatment with coumadin.

Dimeric Her2-Specific Affibody Mediated Cisplatin-Loaded Nanoparticles for Tumor Enhanced Chemo-Radiotherapy

2021 ◽  
Author(s):  
Haijun Wang ◽  
Dianlong Jia ◽  
Dandan Yuan ◽  
Xiaolei Yin ◽  
Fengjiao Yuan ◽  
...  
Keyword(s):  
Ionizing Radiation ◽  
Tumor Cells ◽  
Combined Therapy ◽  
Expression System ◽  
Growth Factor Receptor ◽  
High Energy ◽  
Tumor Growth Inhibition ◽  
Ros Generation ◽  
Her2 Positive

Abstract Background: Solid tumor hypoxic conditions fails to facilitate reactive oxygen species (ROS) generation and formation of DNA double-strand breaks (DSBs) induced by ionizing radiation, ultimately lead to a crucial role in radiotherapy resistance. Recently, there have been significant technical advances in nanomedicine aid to relieve hypoxia by in situ production of O2, serving as “radiosensitizer” to induce tumor cells more sensitive to ionizing radiation. However, the off-target damage of surrounding healthy tissues caused by such high-energy radiation is often unavoidable and the tumor cells at some distance from the focal spot of ionizing radiation may avoid damage. Therefore, there is an urgent need to exploit an intelligently targeted nanoplatform to integrate both precisely enhance RT-induced DNA damage and combined therapy.Results: Herein, we developed human epidermal growth factor receptor 2 (Her2)-specific dimeric affibody (ZHer2) mediated cisplatin-loaded mesoporous polydopamine/MnO2/polydopamine nanoparticles (Pt@mPDA/MnO2/PDA-ZHer2 NPs) for MRI and enhanced chemo-radiotherapy of Her2-positive ovarian tumor. These NPs are biodegradable under simulated tumor microenvironment, resulting in cisplatin accelerated release, as well as production of O2. ZHer2 produced by the E. coli expression system endowed NPs with Her2-dependent binding ability in the Her2-positive SKOV-3 cells. In vivo MRI studies revealed an obvious T1 contrast enhancement at the tumor site. Moreover, these NPs achieved efficient tumor homing and penetration, attributing to the efficient internalization and penetrability of ZHer2. Under X-Ray irradiation, these NPs exhibited the highest tumor growth inhibition effect. Immunofluorescence assay showed these NPs significantly reduced the expression of HIF-1α and improved ROS level, resulting in radiosensitization. Conclusions: The nanocarriers constructed in this study integrated Her2 targeting, diagnosis, RT sensitization, thus providing a new idea for clinical translation in tumor theranostics.

Intratumoral exposure levels of pentaglutamated pemetrexed following treatment with LEAF-1401 and pemetrexed.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 3524-3524
Author(s):  
Gwangseong Kim ◽  
Angelique Nyinawabera ◽  
Zhenghong (Hannah) Xu ◽  
Jason DeFuria ◽  
Alvin Sezibera ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Growth Inhibition ◽  
Tumor Cells ◽  
Xenograft Model ◽  
Fold Increase ◽  
Drug Candidate ◽  
Tumor Growth Inhibition ◽  
Intracellular Enzyme ◽  
Exposure Levels

3524 Background: The activity of pemetrexed is highly dependent on the intracellular enzyme folypolyglutamate synthase (FPGS) which adds glutamates to pemetrexed and yields very potent pemetrexed polyglutamates. Pemetrexed pentaglutamate (tetraglutamated pemetrexed) is 80-fold more potent than pemetrexed in inhibiting thymidylate synthase. Yet it is a poor drug candidate because it cannot readily cross the negatively charged cell membrane due to its own negative charge. We are developing LEAF-1401, a novel nanoliposomal encapsulation of gamma L-pentaglutamated pemetrexed. Because liposomes can readily be taken up by tumor cells, for its anti-tumor effect, LEAF-1401 can directly deliver pentaglutamated pemetrexed into tumor cells, bypassing the need for transmembrane folate carriers and FPGS which are both downregulated in resistant tumors. Methods: To measure drug levels in tumor, blood and various tissues (biodistribution), in vivo testing of LEAF-1401 and pemetrexed was conducted in a CT-26 murine colorectal carcinoma xenograft model. Animals were treated with a single dose of either LEAF-1401 (80mg/kg; equivalent to 32 mg/kg pemetrexed) or pemetrexed (118mg/kg). Tumor growth inhibition and clinical assessments were conducted. Animals were sacrificed: 5 mice per timepoint in each group and tumor, blood, liver, spleen and other tissues were harvested. Pentaglutamated pemetrexed levels were quantitatively analyzed by LC/MS/MS. Results: Compared to pemetrexed, LEAF-1401 treatment resulted in a 19-fold increase in exposure levels of pentaglutamated pemetrexed in the tumor and significant tumor growth inhibition. Plasma levels of pentaglutamated pemetrexed were high with LEAF-1401, but undetectable with pemetrexed. Like other liposomes, LEAF-1401 also resulted in accumulation of pentaglutamated pemetrexed in the liver and spleen (See Table below). Treatment appeared to be generally well tolerated. Conclusions: LEAF-1401, given at approximately a quarter of the equivalent pemetrexed dose, resulted in a 19-fold increase in pentaglutamate pemetrexed in tumor tissue compared to regular pemetrexed. LEAF-1401 represents a promising new class of novel nanoliposomal antifolates, that enhance the intratumoral delivery of potent polyglutamate antifolates, and improve antitumor activity while retaining an acceptable safety profile. [Table: see text]

Dimethylthiourea does not ameliorate reperfusion lung injury in dogs or rabbits

1988 ◽  
Vol 65 (5) ◽  
pp. 2051-2056 ◽  
Author(s):  
M. J. Bishop ◽  
E. Y. Chi ◽  
M. Su ◽  
F. W. Cheney
Keyword(s):  
Hydroxyl Radical ◽  
Rabbit Model ◽  
Left Lung ◽  
Treated Group ◽  
Lung Edema ◽  
Activated Neutrophils ◽  
Pulmonary Arterial ◽  
Species Specific ◽  
The Right

We previously demonstrated that in vivo reperfusion of a dog lung after 48 h of pulmonary arterial (PA) ischemia results in pulmonary edema with a significant infiltrate of polymorphonuclear leukocytes. We hypothesized that the injury resulted from production of hydroxyl radical by activated neutrophils. In the current study, we attempted to prevent the injury in both dogs and rabbits with dimethylthiourea (DMTU), a scavenger of hydroxyl radical. After 48 h of left PA occlusion in 18 dogs, DMTU was administered to 9 animals and 9 were not treated. The occlusion was then released, and the dogs were killed 4 h later. Reperfusion resulted in a drop in leukocyte count and left lung edema, but there was no difference between treated and untreated animals. The wet-to-dry ratios of the lungs in the treated group were 5.76 +/- 0.44 (SE) on the reperfused left side and 4.50 +/- 0.06 (P less than 0.05) on the right side. In the untreated groups the comparable ratios were 5.73 +/- 0.31 and 4.92 +/- 0.10 (P less than 0.05 for right vs. left). Histological examination revealed significant differences between the right and left lungs in the extent of intra-alveolar granulocytes and macrophages but did not reveal differences between the treated and untreated animals. To ensure that neither the model nor the lack of response to DMTU was species specific, we then developed a rabbit model of reperfusion edema.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals In Vivo Tumor Growth Inhibition and Antiangiogenic Effect of Cyclic NGR Peptide-Daunorubicin Conjugates Developed for Targeted Drug Delivery

2019 ◽  
Vol 26 (3) ◽  
pp. 1879-1892 ◽  
Author(s):  
Andrea Angelo Pierluigi Tripodi ◽  
Ivan Ranđelović ◽  
Beáta Biri-Kovács ◽  
Bálint Szeder ◽  
Gábor Mező ◽  
...  
Keyword(s):  
Cell Line ◽  
Tumor Cells ◽  
Tumor Growth Inhibition ◽  
Potential Candidate ◽  
Human Colon Carcinoma Cell ◽  
Antiangiogenic Effect ◽  
Inhibition Of Proliferation ◽  
Ngr Peptide

AbstractAmong various homing devices, peptides containing the NGR tripeptide sequence represent a promising approach to selectively recognize CD13 receptor isoforms on the surface of tumor cells. They have been successfully used for the delivery of various chemotherapeutic drugs to tumor vessels. Here, we report on the murine plasma stability, in vitro and in vivo antitumor activity of our recently described bioconjugates containing daunorubicin as payload. Furthermore, CD13 expression of KS Kaposi’s Sarcoma cell line and HT-29 human colon carcinoma cell line was investigated. Flow cytometry studies confirm the fast cellular uptake resulting in the rapid delivery of the active metabolite Dau = Aoa-Gly-OH to tumor cells. The increased in vitro antitumor effect might be explained by the faster rearrangement from NGR to isoDGR in case of conjugate 2 (Dau = Aoa-GFLGK(c[NleNGRE]-GG)-NH2) in comparison with conjugate 1 (Dau = Aoa-GFLGK(c[KNGRE]-GG)-NH2). Nevertheless, results indicated that both conjugates showed significant effect on inhibition of proliferation in the primary tumor and also on blood vessel formation making them a potential candidate for targeting angiogenesis processes in tumors where CD13 and integrins are involved.

scholarly journals ОСОБЛИВОСТІ ПРОЕКТУВАННЯ НОСКА ПОВІТРОЗАБІРНИКА ТУРБОВЕНТИЛЯТОРНОГО ДВИГУНА

2020 ◽  
pp. 25-36
Author(s):  
Владимир Федорович Шмырев
Keyword(s):  
Shock Wave ◽  
Shock Waves ◽  
Flow Separation ◽  
Sudden Change ◽  
Cross Sectional ◽  
Noise Absorption ◽  
Relevant Task ◽  
Air Intake ◽  
The Right

Optimization of turbofan engine air intake as well as geometry of intake lip, in-let cross-sectional area and its length is a relevant task in optimizing aerodynamic configuration of an aircraft. It is necessary to ensure a smooth entry of air flow into the engine at all modes of its operation and at various aircraft evolutions while minimizing impact on the overall aerodynamic efficiency of the aircraft. Development of engine air intake was once a very long, routine process that could last for months be-fore design completion, followed by expensive tests on determination of air intake performances on the engine test bench and in flight. Today, we can evaluate performances for a large number of air intake options using design software. The use of computational methods does not exclude tests of air intakes but dramatically reduces their quantity, testing costs and allows designers to focus mainly on the best candidates for air intakes avoiding potential surprises such as shock waves or flow separation caused by a shock wave. Optimal design of the air intake includes determining the right balance between the air intake characteristics, structural load and weight. An over-designed air intake will ultimately be overweight and thus more expensive in terms of flight cost. In a well-designed air intake the Mach number should not exceed 1, in order to avoid a sudden change in static pressure, temperature and density, which can lead to potential shock waves and flow separation caused by a shock wave in all areas throughout the flight. The use of computational fluid dynamics al-lows a better understanding of the conditions under which such adverse events occur. Adjacent to this task is the provision of necessary area on the inside of air intake to ensure sufficient noise absorption generated by the engine fan. The article considers evolution of research on the example of air intake of the D-436 engine of the An-148 aircraft.

Minocycline and Cefotaxime in the Treatment of Experimental Murine Vibrio vulnificus Infection

1998 ◽  
Vol 42 (6) ◽  
pp. 1319-1322 ◽  
Author(s):  
Yin-Ching Chuang ◽  
Wen-Chien Ko ◽  
Shan-Tair Wang ◽  
Jien-Wei Liu ◽  
Chih-Feng Kuo ◽  
...  
Keyword(s):  
Vibrio Vulnificus ◽  
Standard Dose ◽  
Survival Rates ◽  
Treated Group ◽  
Inoculum Size ◽  
Control Group ◽  
Human Dose ◽  
The Difference ◽  
The Right

ABSTRACT We conducted an in vivo study with the mouse model of Vibrio vulnificus infection to evaluate the efficacies of therapy with minocycline or cefotaxime alone and in combination. V. vulnificus was introduced subcutaneously into the area over the right thigh. The inoculum size ranged from 1.0 × 103to 1.2 × 108 CFU from experiment to experiment but was constant for all animals in the same experiment. Antibiotics were given intraperitoneally 2 h after the bacteria were inoculated. In experiments 1 to 4, the standard dose for humans was used to treat the infection, while in experiment 5, five times the standard dose for humans was used to treat the infection. In experiment 1, with a small inoculum of 5 × 103 CFU, all mice in the saline-treated control group and the cefotaxime-, minocycline-, and combined antibiotic-treated groups survived. In experiment 2, with a moderate inoculum of 1.2 × 105 CFU, all the mice in the three antibiotic-treated groups survived, while only two of nine mice in the control group survived. In experiment 3, with a large inoculum of 8.0 × 107 CFU, six of nine mice in the combined antibiotic-treated group survived, while only one of nine mice in the cefotaxime-treated group and none of the mice in the control and minocycline-treated groups survived. In experiment 4, with a large inoculum of 1.2 × 108 CFU, 8 of 20 mice in the combined antibiotic-treated group survived, while none of the 20 mice in the control group, the group treated with cefotaxime alone, and the group treated with minocycline alone survived. In experiment 5, in which mice were infected with a large inoculum of 6.6 × 107 CFU and treated with five times the standard human dose of antibiotics, 10 of 12 mice in the combined antibiotic-treated group survived, while only 4 of 12 mice in the minocycline-treated group, 1 of 12 mice in the cefotaxime-treated group, and none of the mice in the control group survived. In experiments 3 to 5, the difference in the survival rates between the combined antibiotic-treated and minocycline-treated groups was statistically significant (P < 0.05). These results indicate that combination therapy with cefotaxime and minocycline is distinctly more advantageous than therapy with the single antibiotic regimen for the treatment of severe experimental V. vulnificus infections.

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