scholarly journals Mathematical modeling of tumor-tumor distant interactions supports a systemic control of tumor growth

2017 ◽  
Author(s):  
Sebastien Benzekry ◽  
Clare Lamont ◽  
Dominique Barbolosi ◽  
Lynn Hlatky ◽  
Philip Hahnfeldt
Keyword(s):  
Tumor Growth ◽  
Growth Control ◽  
Proliferation Inhibition ◽  
Secondary Tumor ◽  
Angiogenesis Inhibition ◽  
Post Surgery ◽  
Distant Interactions ◽  
Global Action ◽  
Single Cancer ◽  
Concomitant Resistance

AbstractInteractions between different tumors within the same organism have major clinical implications, especially in the context of surgery and metastatic disease. Three main explanatory theories (competition, angiogenesis inhibition and proliferation inhibition) have been proposed but precise determinants of the phenomenon remain poorly understood. Here we formalized these theories into mathematical models and performed biological experiments to test them with empirical data. In syngeneic mice bearing two simultaneously implanted tumors, growth of only one of the tumors was significantly suppressed (61% size reduction at day 15, p<0.05). The competition model had to be rejected while the angiogenesis inhibition and proliferation inhibition models were able to describe the data. Additional models including a theory based on distant cytotoxic log-kill effects were unable to fit the data. The proliferation inhibition model was identifiable and minimal (4 parameters), and its descriptive power was validated against the data, including consistency in predictions of single tumor growth when no secondary tumor was present. This theory may also shed new light on single cancer growth insofar as it offers a biologically translatable picture of how local and global action may combine to control local tumor growth, and in particular, the role of tumor-tumor inhibition. This model offers a depiction of concomitant resistance that provides an improved theoretical basis for tumor growth control and may also find utility in therapeutic planning to avoid post-surgery metastatic acceleration.

Abstract B145: Addition of galunisertib to DC101 improved angiogenesis inhibition and tumor growth control in hepatocellular carcinoma (HCC)

2018 ◽  
Author(s):  
Annemilai Tijeras-Raballand ◽  
Christian Hobeika ◽  
Matthieu Martinet ◽  
Elise Paven ◽  
Philippe Bonin ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Tumor Growth ◽  
Growth Control ◽  
Angiogenesis Inhibition

Abstract 29: Addition of Galunisertib to DC101 increased angiogenesis inhibition and tumor growth control in hepatocellular carcinoma (HCC)

2017 ◽  
Author(s):  
Annemilai Tijeras-Raballand ◽  
Christian Hobeika ◽  
Elise Payen ◽  
Matthieu Martinet ◽  
Philippe Bonnin ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Tumor Growth ◽  
Growth Control ◽  
Angiogenesis Inhibition

scholarly journals A Tumor-Peptide–Based Nanoparticle Vaccine Elicits Efficient Tumor Growth Control in Antitumor Immunotherapy

2019 ◽  
Vol 18 (6) ◽  
pp. 1069-1080 ◽  
Author(s):  
Carolin Heße ◽  
Sebastian Kollenda ◽  
Olga Rotan ◽  
Eva Pastille ◽  
Alexandra Adamczyk ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Growth Control ◽  
Antitumor Immunotherapy

Gamma Knife Radiosurgery for the Treatment of Cavernous Sinus Meningiomas

Neurosurgery ◽  
2003 ◽  
Vol 52 (3) ◽  
pp. 517-524 ◽  
Author(s):  
Yoshiyasu Iwai ◽  
Kazuhiro Yamanaka ◽  
Tomoya Ishiguro
Keyword(s):  
Tumor Growth ◽  
Gamma Knife ◽  
Cavernous Sinus ◽  
Tumor Regression ◽  
Gamma Knife Radiosurgery ◽  
Growth Control ◽  
Neurological Deficits ◽  
Surgical Removal ◽  
Tumor Diameter

Abstract OBJECTIVE We report on the efficacy of gamma knife radiosurgery for cavernous sinus meningiomas. METHODS Between January 1994 and December 1999, we used gamma knife radiosurgery for the treatment of 43 patients with cavernous sinus meningiomas. Forty-two patients were followed up for a mean of 49.4 months (range, 18–84 mo). The patients' average age was 55 years (range, 18–81 yr). Twenty-two patients (52%) underwent operations before radiosurgery, and 20 patients (48%) underwent radiosurgery after the diagnosis was made by magnetic resonance imaging. The tumor volumes ranged from 1.2 to 101.5 cm3 (mean, 14.7 cm3). The tumors either compressed or were attached to the optic apparatus in 17 patients (40.5%). The marginal radiation dose was 8 to 15 Gy (mean, 11 Gy), and the optic apparatus was irradiated with 2 to 12 Gy (mean, 6.2 Gy). Three patients with a mean tumor diameter greater than 4 cm were treated by two-stage radiosurgery. RESULTS Thirty-eight patients (90.5%) demonstrated tumor growth control during the follow-up period after radiosurgery. Tumor regression was observed in 25 patients (59.5%), and growth was unchanged in 13 patients (31%). Regrowth or recurrence occurred in four patients (9.5%). The actual tumor growth control rate at 5 years was 92%. Only one patient (2.4%) experienced regrowth within the treatment field; in other patients, regrowth occurred at sites peripheral to or outside the treatment field. Twelve patients (28.6%) had improved clinically by the time of the follow-up examination. None of the patients experienced optic neuropathy caused by radiation injury or any new neurological deficits after radiosurgery. CONCLUSION Gamma knife radiosurgery may be a useful option for the treatment of cavernous sinus meningiomas not only as an adjuvant to surgery but also as an alternative to surgical removal. We have shown it to be safe and effective even in tumors that adhere to or are in close proximity to the optic apparatus.

scholarly journals Association of cathepsin E with tumor growth arrest through angiogenesis inhibition and enhanced immune responses

2007 ◽  
Vol 388 (11) ◽  
Author(s):  
Masashi Shin ◽  
Tomoko Kadowaki ◽  
Jun-ichi Iwata ◽  
Tomoyo Kawakubo ◽  
Noriko Yamaguchi ◽  
...  
Keyword(s):  
Immune Responses ◽  
Tumor Growth ◽  
Growth Arrest ◽  
Angiogenesis Inhibition ◽  
Cathepsin E

DNA repair inhibition by DT01 as an adjuvant therapy at each stage of hepatocellular cancer (HCC) treatment.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 303-303
Author(s):  
Flavien Devun ◽  
Nirmitha Herath ◽  
Alban Denys ◽  
Jian-sheng Sun ◽  
Marie Dutreix
Keyword(s):  
Hepatocellular Carcinoma ◽  
Dna Damage ◽  
Adjuvant Therapy ◽  
Tumor Growth ◽  
Median Survival ◽  
Tumor Necrosis ◽  
Liver Tumors ◽  
Color Doppler ◽  
Growth Control ◽  
Hepatocellular Cancer

303 Background: Hepatocellular carcinoma (HCC) is the most common liver cancer. Radiofrequency ablation (RFA), transarterial chemoembolization (TACE) or chemotherapy (CT) can be considered at each stage of HCC. The efficacy of these DNA damage inducing treatments could be enhanced by DNA damage repair inhibition. DT01 inhibits the complete DNA double-strand break repair machinery. Here, we assess the combination of DT01 with RFA, TACE or CT in preclinical models. Methods: For association with RFA, mice bearing flank-grafted tumors were sham treated (n=18), treated by DT01 (n=22), RFA (n=21) or a combination of DT01 and RFA (n=19). Mice were either sacrificed for pathological study or followed for survival. For association with TACE, rabbits bearing VX2 hepatocellular carcinoma in liver were untreated (n=9), treated with TACE (n=13) or treated with TACE and DT01 (n=14). Tumor growth, vascularization, necrosis and metastases were assessed with ultrasound scanning, color Doppler, pathology and autopsy respectively. For association with CT, mice bearing orthotopic liver tumors were administered NaCl (n=7), CT (doxorubicin) (n=10), systemic DT01 treatment (n=7) or an association of DT01 and CT (n=10). Tumor growth and pathological studies were assessed. Results: Mice treated by RFA and DT01 have longer survival compared to RFA alone (median survival: 57 vs 40 days) with 54% of complete responses while RFA alone improved survival moderately (median survival: 40 vs 28 days for control). Rabbits treated with TACE and DT01, in comparison to CT alone, show efficient tumor growth control, an increase of tumor necrosis (61% vs 40%), a decrease of metastases (21 vs 54%) and an absence of neoangiogenesis rebound. Mice treated with CT in combination with DT01 show a significant decrease in tumor volume and tumor necrosis, compared to the mice treated with CT alone. In all models, DT01 addition to treatments did not add any toxicity. Conclusions: Our results show that the addition of DT01 to RFA, TACE or CT enhances their antitumor activities and provide an experimental basis for the use of DT01 as an adjuvant therapy at each stage of HCC treatment.

Radiosurgery for Acoustic Neuromas: Results of Low-dose Treatment

Neurosurgery ◽  
2003 ◽  
Vol 53 (2) ◽  
pp. 282-288 ◽  
Author(s):  
Yoshiyasu Iwai ◽  
Kazuhiro Yamanaka ◽  
Masato Shiotani ◽  
Taichi Uyama
Keyword(s):  
Tumor Growth ◽  
Low Dose ◽  
Tumor Resection ◽  
Gamma Knife Radiosurgery ◽  
Growth Control ◽  
Hearing Preservation ◽  
Trigeminal Neuropathy ◽  
Tumor Margin ◽  
Acoustic Neuromas

Abstract OBJECTIVE The results of radiosurgical treatment of acoustic neuromas have improved by reducing the tumor marginal doses. We report relatively long-term follow-up results (&gt;5 yr) for patients who underwent low-dose radiosurgery. METHODS We treated and followed 51 consecutive patients with unilateral acoustic neuromas who were treated from January 1994 to December 1996 by gamma knife radiosurgery at low doses (≤12 Gy to the tumor margin). The average age of the patients was 55 years (range, 32–76 yr). The treatment volume was 0.7 to 24.9 cm3 (median, 3.6 cm3). The marginal radiation dose was 8 to 12 Gy (median, 12 Gy), and the follow-up period ranged from 18 to 96 months (median, 60 mo). RESULTS Clinical tumor growth control (without tumor resection) was achieved in 96% of patients, and the 5-year tumor growth control rate was 92%. Hearing was preserved in 59% of those with preradiosurgical hearing preservation (Gardner-Robertson Classes 1–4), and improvements (&gt;20 dB of improvement) were noted in 9% of the patients with any hearing. Hearing was preserved at a useful level (Gardner-Robertson Classes 1 and 2) in 56% of patients. Although preexisting trigeminal neuropathy worsened in 4% of the patients, our patients did not experience new facial palsies or trigeminal neuropathies after radiosurgery. Facial spasm occurred in 6% of the patients, and intratumoral bleeding occurred in 4% of patients. CONCLUSION Low-dose radiosurgery (≤12 Gy at the tumor margin) can achieve a high tumor growth control rate and maintain low postradiosurgical morbidity (including hearing preservation) for acoustic neuromas.

Galectins: their network and roles in immunity/tumor growth control

2016 ◽  
Vol 147 (2) ◽  
pp. 239-256 ◽  
Author(s):  
Herbert Kaltner ◽  
Stefan Toegel ◽  
Gabriel García Caballero ◽  
Joachim C. Manning ◽  
Robert W. Ledeen ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Growth Control

scholarly journals Combinations of TLR Ligands: A Promising Approach in Cancer Immunotherapy

2013 ◽  
Vol 2013 ◽  
pp. 1-14 ◽  
Author(s):  
Saskia Stier ◽  
Claudia Maletzki ◽  
Ulrike Klier ◽  
Michael Linnebacher
Keyword(s):  
Tumor Growth ◽  
Tumor Cells ◽  
Cell Lines ◽  
Immune Cells ◽  
Human Lymphocytes ◽  
Growth Control ◽  
Poly I:C ◽  
The Impact

Toll-like receptors (TLRs), a family of pattern recognition receptors recognizing molecules expressed by pathogens, are typically expressed by immune cells. However, several recent studies revealed functional TLR expression also on tumor cells. Their expression is a two-sided coin for tumor cells. Not only tumor-promoting effects of TLR ligands are described but also direct oncopathic and immunostimulatory effects. To clarify TLRs’ role in colorectal cancer (CRC), we tested the impact of the TLR ligands LPS, Poly I:C, R848, and Taxol on primary human CRC cell lines (HROC40, HROC60, and HROC69)in vitroandin vivo(CT26). Taxol, not only a potent tumor-apoptosis-inducing, but also TLR4-activating chemotherapeutic compound, inhibited growth and viability of all cell lines, whereas the remaining TLR ligands had only marginal effects (R848 > LPS > Poly I:C). Combinations of the substances here did not improve the results, whereas antitumoral effects were dramatically boosted when human lymphocytes were added. Here, combining the TLR ligands often diminished antitumoral effects.In vivo, best tumor growth control was achieved by the combination of Taxol and R848. However, when combined with LPS, Taxol accelerated tumor growth. These data generally prove the potential of TLR ligands to control tumor growth and activate immune cells, but they also demonstrate the importance of choosing the right combinations.

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