scholarly journals p53-Mediated Radiosensitization of 177Lu-DOTATATE in Neuroblastoma Tumor Spheroids

Biomolecules ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. 1695
Author(s):  
Sara Lundsten ◽  
Hanna Berglund ◽  
Preeti Jha ◽  
Cecilia Krona ◽  
Mehran Hariri ◽  
...  
Keyword(s):  
Combination Treatment ◽  
Synergistic Effects ◽  
Neuroblastoma Cell ◽  
Somatostatin Receptors ◽  
Treatment Modalities ◽  
Tumor Spheroids ◽  
Combination Treatments ◽  
Neuroblastoma Tumor ◽  
Ic50 Values ◽  
Fold Induction

p53 is involved in DNA damage response and is an exciting target for radiosensitization in cancer. Targeted radionuclide therapy against somatostatin receptors with 177Lu-DOTATATE is currently being explored as a treatment for neuroblastoma. The aim of this study was to investigate the novel p53-stabilizing peptide VIP116 in neuroblastoma, both as monotherapy and together with 177Lu-DOTATATE. Five neuroblastoma cell lines, including two patient-derived xenograft (PDX) lines, were characterized in monolayer cultures. Four out of five were positive for 177Lu-DOTATATE uptake. IC50 values after VIP116 treatments correlated with p53 status, ranging between 2.8–238.2 μM. IMR-32 and PDX lines LU-NB-1 and LU-NB-2 were then cultured as multicellular tumor spheroids and treated with 177Lu-DOTATATE and/or VIP116. Spheroid growth was inhibited in all spheroid models for all treatment modalities. The most pronounced effects were observed for combination treatments, mediating synergistic effects in the IMR-32 model. VIP116 and combination treatment increased p53 levels with subsequent induction of p21, Bax and cleaved caspase 3. Combination treatment resulted in a 14-fold and 1.6-fold induction of MDM2 in LU-NB-2 and IMR-32 spheroids, respectively. This, together with differential MYCN signaling, may explain the varying degree of synergy. In conclusion, VIP116 inhibited neuroblastoma cell growth, potentiated 177Lu-DOTATATE treatment and could, therefore, be a feasible treatment option for neuroblastoma.

Combination Treatment With Trabectedin and Irinotecan or Topotecan Has Synergistic Effects Against Ovarian Clear Cell Carcinoma Cells

2014 ◽  
Vol 24 (5) ◽  
pp. 829-837 ◽  
Author(s):  
Mahiru Kawano ◽  
Seiji Mabuchi ◽  
Toshiko Kishimoto ◽  
Takeshi Hisamatsu ◽  
Yuri Matsumoto ◽  
...  
Keyword(s):  
Cell Carcinoma ◽  
Cell Lines ◽  
Combination Treatment ◽  
Clear Cell ◽  
Clear Cell Carcinoma ◽  
Synergistic Effects ◽  
Chemotherapeutic Agents ◽  
Ovarian Clear Cell Carcinoma ◽  
Combination Treatments

ObjectivesThe objective of this study was to investigate the chemotherapeutic agents that produce the strongest synergistic effects when combined with trabectedin against ovarian clear cell carcinoma (CCC), which is regarded as an aggressive chemoresistant histological subtype.MethodsUsing 4 human CCC cell lines (RMG1, RMG2, KOC7C, and HAC2), the cytotoxicities of trabectedin, SN-38, topotecan, doxorubicin, cisplatin, and paclitaxel as single agents were first assessed using the MTS assay. Then, the cytotoxicities of combination treatments involving trabectedin and 1 of the other 4 agents were evaluated by isobologram analysis to examine whether these combinations displayed synergistic, additive, or antagonistic effects. The antitumor activities of the combination treatments were also examined using cisplatin-resistant and paclitaxel-resistant CCC sublines, which were derived from the parental CCC cells by continuously exposing them to cisplatin or paclitaxel. Finally, we determined the effect of everolimus on the antitumor efficacy of trabectedin-based combination chemotherapy.ResultsConcurrent exposure to trabectedin and SN-38 or topotecan resulted in synergistic interactions in all 4 CCC cell lines. Among the tested combinations, trabectedin plus SN-38 was the most effective cytotoxic regimen. The combination of trabectedin plus SN-38 also had strong synergistic effects on both the cisplatin-resistant and paclitaxel-resistant CCC cell lines. Treatment with everolimus significantly enhanced the antitumor activity of trabectedin plus SN-38 or topotecan.ConclusionsCombination treatment with trabectedin and SN-38 displays the greatest cytotoxic effect against ovarian CCC. Our in vitro study provides the rationale for future clinical trials of trabectedin plus irinotecan with or without everolimus in patients with ovarian CCC in both the front-line chemotherapy setting and as a second-line treatment of recurrent CCC that had previously been treated with cisplatin or paclitaxel.

Effect of Growth Regulators on Rooting of Magnolia grandifloraCultivars

HortScience ◽  
1998 ◽  
Vol 33 (3) ◽  
pp. 503d-503
Author(s):  
Ning Jiang ◽  
Donglin Zhang ◽  
Michael A. Dirr
Keyword(s):  
Growth Regulators ◽  
Combination Treatment ◽  
Similar Response ◽  
Combination Treatments ◽  
Rooting Of Cuttings ◽  
Root Quality

Cuttings from three southern magnolia cultivars, `Claudia Wannamaker', `Greenback™', and `Little Gem', were treated with KIBA, KNAA, and Hormodin #3, separately and in combination, at varying concentrations. The rooting of cuttings was cultivar-dependent, with `Greenback™' responding significantly to all the treatments. Only the high KNAA and combination treatments were effective with `Little Gem' and `Claudia Wannamaker'. The effect of KNAA on rooting with increasing concentration was significant. No similar response was observed with KIBA. The combination treatment with quick dip plus the talc formation produced the greatest rooting and root quality with the three cultivars. With this treatment, the average rooting rate of three cultivars was 67.4%, whereas the rooting rate of control plants was only 11.8%.

scholarly journals Anticancer effects of the combined Thai noni juice ethanolic extracts and 5-fluorouracil against cholangiocarcinoma cells in vitro and in vivo

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jeerati Prompipak ◽  
Thanaset Senawong ◽  
Banchob Sripa ◽  
Albert J. Ketterman ◽  
Suppawit Utaiwat ◽  
...  
Keyword(s):  
Nude Mice ◽  
Combination Treatment ◽  
Synergistic Effects ◽  
Single Agent ◽  
Xenograft Model ◽  
Ethanolic Extract ◽  
Model Combination ◽  
Mouse Xenograft Model ◽  
Ethanolic Extracts

AbstractApplication of 5-fluorouracil (5-FU) in cholangiocarcinoma (CCA) is limited by adverse side effects and chemoresistance. Therefore, the combination therapy of 5-FU with other substances, especially natural products may provide a new strategy for CCA treatment. The aim of this study was to evaluate the combination effects of 5-FU and two ethanolic extracts of Thai noni juice (TNJ) products on CCA cell lines and nude mice xenografts. The results of antiproliferative assay showed the combination treatment of 5-FU and each TNJ ethanolic extract exerted more cytotoxicity on CCA cells than either single agent treatment. Synergistic effects of drug combinations can enable the dose reduction of 5-FU. The mechanism underlying a combination treatment was apoptosis induction through an activation of p53 and Bax proteins. In the nude mouse xenograft model, combination treatments of 5-FU with each TNJ ethanolic extract suppressed the growth of CCA cells implanted mice more than single agent treatments with no effects on mouse body weight, kidney, and spleen. Moreover, low doses of TNJ ethanolic extracts reduced the hepatotoxicity of 5-FU in nude mice. Taken together, these data suggested that the ethanolic extracts of TNJ products can enhance the anti-CCA effect and reduce toxicity of 5-FU.

scholarly journals Combination of Modified Atmosphere and Irradiation for the Phytosanitary Disinfestation of Trogoderma granarium Everts (Coleoptera: Dermestidae)

Insects ◽  
2021 ◽  
Vol 12 (5) ◽  
pp. 442
Author(s):  
Qing-Ying Zhao ◽  
Tian-Xiu Li ◽  
Zi-Jiao Song ◽  
Tao Sun ◽  
Bo Liu ◽  
...  
Keyword(s):  
Late Stage ◽  
Synergistic Effects ◽  
Combined Treatment ◽  
Modified Atmosphere ◽  
Trogoderma Granarium ◽  
Combination Treatments ◽  
Phytosanitary Measure ◽  
Ma Packaging ◽  
Confirmatory Tests ◽  
Lethal Time

The khapra beetle, Trogoderma granarium Everts, is defined as one of the most important quarantine pests globally, and fumigation with methyl bromide, an ozone-depleting substance, is a common phytosanitary measure currently used. The modified atmosphere (MA), irradiation, and their combination treatments of T. granarium larvae and adults were performed at room temperature (24–26 ℃) to develop an ecofriendly phytosanitary disinfestation measure and to shorten the exposure time and overcome treatment disadvantages of irradiation. Late-stage larvae are determined as the most tolerant stage resulted in large LT99.9968 values of 32.6 (29.2–37.5) and 38.0 (35.1–41.7) days treated under 1% and 2% O2 (with N2 balance) atmosphere, respectively. Ionizing radiation was used to enhance the effect of MA and the mortality was highly significantly affected by all the interaction effects, indicating that the synergistic effects present in all the combined treatments. The synergistic ratios, which is defined as the estimated lethal time for MA treatment (LD90, LD99, and LD99.9968), divided by that of combined treatment, were between 1.47 and 2.47. In the confirmatory tests, no individuals recovered from a sum of 111,366 late-stage larvae treated under 1% O2 atmosphere for 14- or 15-d after 200 Gy irradiation, which resulted in validating the probit estimations and achieving an efficacy of 99.9973% mortality at 95% confidence level. Therefore, these treatment schedules are recommended to disinfest T. granarium infecting commodities for phytosanitary purposes under the warehouse, MA packaging, or in combination with international transportation by train or sea container.

scholarly journals Indications of Peptide Receptor Radionuclide Therapy (PRRT) in Gastroenteropancreatic and Pulmonary Neuroendocrine Tumors: An Updated Review

2021 ◽  
Vol 10 (6) ◽  
pp. 1267
Author(s):  
Baptiste Camus ◽  
Anne-Ségolène Cottereau ◽  
Lola-Jade Palmieri ◽  
Solène Dermine ◽  
Florence Tenenbaum ◽  
...  
Keyword(s):  
Neuroendocrine Tumors ◽  
Radionuclide Therapy ◽  
Somatostatin Receptors ◽  
Peptide Receptor Radionuclide Therapy ◽  
Phase Iii ◽  
Treatment Modalities ◽  
High Dose ◽  
Double Dose ◽  
Peptide Receptor ◽  
Phase Iii Study

Radionuclide therapy for neuroendocrine tumors is a form of systemic radiotherapy that allows the administration of targeted radionuclides into tumor cells that express a large quantity of somatostatin receptors. The two most commonly used radio-peptides for radionuclide therapy in neuroendocrine tumors are 90Y-DOTATOC and 177Lu-DOTATATE. Radio-peptides have been used for several years in the treatment of advanced neuroendocrine tumors. Recently, the randomized Phase III study NETTER-1 compared177Lu-DOTATATE versus high-dose (double-dose) octreotide LAR in patients with metastatic midgut neuroendocrine tumors, and demonstrated its efficacy in this setting. Strong signals in favor of efficiency seem to exist for other tumors, in particular for pancreatic and pulmonary neuroendocrine tumors. This focus on radionuclide therapy in gastroenteropancreatic and pulmonary neuroendocrine tumors addresses the treatment modalities, the validated and potential indications, and the safety of the therapy.

scholarly journals N-Dihydrogalactochitosan Potentiates the Radiosensitivity of Liver Metastatic Tumor Cells Originated from Murine Breast Tumors

2019 ◽  
Vol 20 (22) ◽  
pp. 5581
Author(s):  
Chung-Yih Wang ◽  
Chun-Yuan Chang ◽  
Chun-Yu Wang ◽  
Kaili Liu ◽  
Chia-Yun Kang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Synergistic Effects ◽  
Metastatic Breast ◽  
Treatment Modalities ◽  
X Rays ◽  
Dna Breaks ◽  
4T1 Cells ◽  
4T1 Breast Cancer

Radiation is a widely used therapeutic method for treating breast cancer. N-dihydrogalactochitosan (GC), a biocompatible immunostimulant, is known to enhance the effects of various treatment modalities in different tumor types. However, whether GC can enhance the radiosensitivity of cancer cells remains to be explored. In this study, triple-negative murine 4T1 breast cancer cells transduced with multi-reporter genes were implanted in immunocompetent Balb/C mice to track, dissect, and identify liver-metastatic 4T1 cells. These cells expressed cancer stem cell (CSC) -related characteristics, including the ability to form spheroids, the expression of the CD44 marker, and the increase of protein stability. We then ex vivo investigated the potential effect of GC on the radiosensitivity of the liver-metastatic 4T1 breast cancer cells and compared the results to those of parental 4T1 cells subjected to the same treatment. The cells were irradiated with increased doses of X-rays with or without GC treatment. Colony formation assays were then performed to determine the survival fractions and radiosensitivity of these cells. We found that GC preferably increased the radiosensitivity of liver-metastatic 4T1 breast cancer cells rather than that of the parental cells. Additionally, the single-cell DNA electrophoresis assay (SCDEA) and γ-H2AX foci assay were performed to assess the level of double-stranded DNA breaks (DSBs). Compared to the parental cells, DNA damage was significantly increased in liver-metastatic 4T1 cells after they were treated with GC plus radiation. Further studies on apoptosis showed that this combination treatment increased the sub-G1 population of cells, but not caspase-3 cleavage, in liver-metastatic breast cancer cells. Taken together, the current data suggest that the synergistic effects of GC and irradiation might be used to enhance the efficacy of radiotherapy in treating metastatic tumors.

Palliative Treatment of Hyperinsulinism With Cyproheptadine and Diazoxide

PEDIATRICS ◽  
1992 ◽  
Vol 90 (2) ◽  
pp. 212-215
Author(s):  
Deborah Rotenstein ◽  
Scott Serbin ◽  
Terra Welsh
Keyword(s):  
Glucose Level ◽  
Combination Treatment ◽  
Palliative Treatment ◽  
Neonatal Period ◽  
Insulin Level ◽  
Treatment Modalities ◽  
Normal Range ◽  
C Peptide ◽  
Level Of Consciousness ◽  
In Infants And Children

Treatment for hyperinsulinism in infants and children can be difficult and has included numerous treatment modalities. This paper reports 16 months of palliative treatment with cyproheptadine and diazoxide in a child with hyperinsulinism initially diagnosed at 6 months of age (her insulin level was 80 µU/mL while her glucose level was 38 mg/dL). She continued to have episodes of staring and alteration in level of consciousness while receiving her usual doses of diazoxide (12 mg/kg) alone. Mean nocturnal glucose values, which were quite low during treatment with diazoxide alone, improved significantly with the addition of cyproheptadine to her therapeutic regimen. Fasted C-peptide values, elevated during diazoxide alone, returned to the normal range with combination treatment for 16 months. Cyproheptadine and diazoxide in combination may be useful for treatment of hyperinsulinism that presents after the neonatal period.

scholarly journals DEVELOPMENT OF NANOPARTICULATE DRUG DELIVERY SYSTEM FROM MARINE SOURCE AGAINST HUMAN IMMUNODEFICIENCY VIRUS

2019 ◽  
pp. 38-40
Author(s):  
HARIKRISHNAN N ◽  
ANAS S MOHAMIED ◽  
GEJALAKSHMI S
Keyword(s):  
Human Immunodeficiency Virus ◽  
Protein Separation ◽  
Chemical Method ◽  
Inhibitory Concentration ◽  
Treatment Modalities ◽  
Standard Drug ◽  
Immunodeficiency Virus ◽  
Ic50 Values ◽  
Infection Inhibition ◽  
Anti Hiv

Objective: Nanotechnology techniques are a creation and exploitation of materials, devices, and systems through the control of matter on the nanometer length scale, i.e., involvement of atoms, molecules, and supramolecular structures. Every existing treatment modalities against human immunodeficiency virus (HIV) offer a marginal increase in the life expectancy as chitosan was converted to its derivative aminoethyl chitosan by chemical method evaluated for anti-HIV activity. Methods: Isolation of chitosan from crab shell by chemical method involves four basic steps; protein separation, calcium carbonate separation, deproteinization, and demineralization. Results: The results revealed the anti-HIV activity of the prepared nanoparticulate system. Cytotoxicity assay of the nanoparticulate system was carried out and the cytotoxic concentration 50% (CC50) value was found to be 38.07±1.42 μg/ml, indicating that the nanoparticulate system is not cytotoxic. HIV-1 infection inhibition assay was carried out and the nanoparticulate system showed excellent inhibitory activity with a half-maximal inhibitory concentration (IC50) value of 3.75±0.57 μg/ml. Conclusions: It concludes, the CC50 and inhibitory concentration 50% IC50 values, the selectivity index of the nanoparticle was found to be 17.65 compared to the standard drug nevirapine (82.32), indicating the usefulness of the formulated nanoparticulate system as potential anti-HIV agent.

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