Effect Of Different Treatment Regimens Research Articles

Abstract 1911: NF-κB mediated CD47 upregulation promotes sorafenib resistance and its blockade synergizes the effect of sorafenib in hepatocellular carcinoma

Abstract Sorafenib, a multikinase inhibitor, is currently used as the normative treatment for advanced hepatocellular carcinoma (HCC). It can prolong survival for a few months however sorafenib insensitivity and resistance often develops in tumors hence a better understanding of resistance mechanisms is urgently needed. Tumor-initiating cells (T-ICs) have recently been implicated in the cause of treatment resistance. Recently, our group found that CD47 is preferentially expressed in liver T-ICs, which suggests a possibility of targeting CD47 in order to evade sorafenib resistance via elimination of liver T-ICs. To test this hypothesis, we have successfully developed sorafenib-resistant clones in HCC cell lines (BEL7402 and Huh-7 cells) and in vivo using patient-derived xenograft (PDTX #1) by continuous exposure to sorafenib. We found that sorafenib-resistant clones showed enhanced T-IC properties such as self-renewal, tumorigenicity and invasiveness, which is also accompanied by an increase in CD47 expression. We found increased NF-κB activation in sorafenib resistant clones indicated by upregulated levels of phosphorylated p65 and IkBα which is consistent to the bioinformatics analysis showing two putative NF-κB binding sites on the CD47 promoter. In addition, CD47 expression was found to be decreased upon treatment of NF-κB inhibitor IMD-0354 and increased upon treatment of TNF-α. These results suggested that NF-κB mediated CD47 upregulation promotes sorafenib resistance in HCC. To further confirm the role of CD47 in sorafenib resistance, we knocked down CD47 expression in CD47-high expressing HCC cells. Through annexin V staining, we found that knockdown of CD47 sensitized Huh-7 and MHCC-97L to sorafenib treatment at 10µM and 20µM respectively. Using patient derived xenograft model (PDTX #8) to investigate the effect of different treatment regimens, we found that mice treated with daily administration of sorafenib (100mg/Kg) showed tumor volume reduction by 3-fold upon 30 days of treatment and a similar effect was found in mice treated daily with and anti-CD47 antibody (500mg/Kg). Interestingly, sorafenib combined with anti-CD47 antibody exhibited maximal effect on tumor suppression. All in all, regulation of CD47 by NF-κB may enable the promotion of sorafenib resistance and anti-CD47 antibody in co-treatment with sorafenib may serve as a novel therapeutic regimen for the treatment of advanced stage HCC. Citation Format: Jessica Lo, Eunice Yuen Ting Lau, Irene Oi Lin Ng, Terence Kin Wah Lee. NF-κB mediated CD47 upregulation promotes sorafenib resistance and its blockade synergizes the effect of sorafenib in hepatocellular carcinoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1911. doi:10.1158/1538-7445.AM2014-1911

The development and validation of oral cancer staging using administrative health data.

BackgroundOral cancer is a major global health problem. The complexity of histological prognosticators in oral cancer makes it difficult to compare the benefits of different treatment regimens. The Taiwanese National Health database provides an opportunity to assess correlations between outcome and treatment protocols and to compare the effects of different treatment regimens. However, the absence of indices of disease severity is a critical problem. The aim of this study was to ascertain how accurately we could assess the severity of oral cancer at the time of initial diagnosis on the basis of variables in a national database.MethodsIn the cancer registry database of a medical center in Taiwan, we identified 1067 histologically confirmed cases of oral cancer (ICD9 codes 140, 141 and 143–145) that had been first diagnosed and subjected to initial treatment in this hospital. The clinical staging status was considered as the gold standard and we used concordance (C)-statistics to assess the model’s predictive performance. We added the predictors of treatment modality, cancer subsite, and age group to our models.ResultsOur final overall model included treatment regimen, site, age, and two interaction terms; namely, interactions between treatment regimen and age and those between treatment regimen, site, and age. In this model, the C-statistics were 0.82–0.84 in male subjects and 0.96–0.99 in female subjects. Of the models stratified by age, the model that considered treatment regimen and site had the highest C-statistics for the interaction term, this value being greater than 0.80 in male subjects and 0.9 in female subjects.ConclusionIn this study, we found that adjusting for sex, age at first diagnosis, oral cancer subsite, and therapy regimen provided the best indicator of severity of oral cancer. Our findings provide a method for assessing cancer severity when information about staging is not available from a national health-related database.

PCN111 - Cost-Effectiveness Analysis of Bevacizumab in Combination with PC Regimen Versus PC Regimen in Non-Small Cell Lung Cancer Treatment

Fabulous advance in treatment of NSCLC has been made since the late 1990s, remarkably with the development of targeted drugs such as bevacizumab (BEV). Despite of the proved effectiveness and safety of BEV in treatment of NSCLC, the high price of drug caused obstacles in using drugs in clinical practice. The cost-effectiveness of BEV has been evaluated in many countries. However until now there isn’t any relevant study has been evaluated. This is the aim of this study. A Markov model has been developed to evaluate the cost-effectiveness of bevacizumab in treatment of NSCLC with 3 Markov stages, including stable disease, progressive disease and death. The model has a cycle length of 1 year with the time horizon of life time. The population of 1000 patients patients, entering the model in the SD state, has been evaluated to assess the cost of effectiveness of different treatment regimens. The transition rates have been retrieved from clinical trials. The prices of drugs and medical services have been retrieved from relevant price-lists of major hospitals in Vietnam. The sensitivity analysis has been conducted to evaluate the sensitivity of model. The cost of BCP and PC regimen for treatment of NSCLC accounts for 5,979,573,560 VND and 992,767,115 with the QALY of 10.43 and 7.24, respectively. The CER of BCP regimens for treatment of NCSLC accounts for 573,199,170 VND, which is around 4 times higher than that of PC regimen. The ICER of BCP regimen versus PC regimen in treatment of NSCLC accounts for around 1.56 billion VND, which is around 20 times higher than the willingness-to-pay of Vietnam (60 million VND). Due to the high cost of drug, combination of bevacizumab in the PC regimen in treatment of NSCLC is considered not cost-effectiven in Vietnam.

Interleukin‐15 gene therapy and the mammalian target of rapamycin inhibitor everolimus inhibit the growth of metastatic breast cancer

Novel methods to control and treat metastatic breast cancer are needed. Interleukin (IL)-15 is a promising cytokine for cancer immunotherapy, and everolimus is an orally administered mammalian target of rapamycin (mTOR) inhibitor, which is already approved for cancer treatment. In the present study, we investigated the efficacy of IL-15 gene therapy and explored the possibility of combining IL-15 therapy with everolimus to treat metastatic breast cancer. A plasmid encoding IL-15 and everolimus were given to mice inoculated with 4 T1 mouse breast cancer cells. Tumor size and metastasis were monitored to assess the effect of different treatment regimens. Immunohistochemistry was used to detect CD4⁺, CD8⁺ and NKG2D⁺ cells and also the expression of Ki-67 in tumor tissue; these analyses helped establish the immunization status and tumor proliferation rate of different treatment groups. Terminal deoxynucleotidyl transferase dUTP nick end labeling assays were performed to assess cellular apoptosis in tumor tissues. Both IL-15 and everolimus significantly decreased tumor size. IL-15 gene therapy increased the proportion of CD4⁺ T and natural killer (NK) cells but had no effect on CD8⁺ T cells. By contrast, everolimus decreased the number of CD8⁺ T cells but had no effect on CD4⁺ T and NK cells compared to the control group. Both IL-15 and everolimus decreased expression of Ki-67 and increased rates of apoptosis. Although effective on their own, no synergistic effect was observed with a combined treatment of everolimus and IL-15 gene therapy. IL-15 gene therapy was potentially useful for the treatment of metastatic breast cancer. The possibility of combining immunotherapy with everolimus requires further study.

261 Effect of different treatment regimens of CFRD on clinical status: A register study

261 Effect of different treatment regimens of CFRD on clinical status: A register study

Natural History and Molecular Characteristics of Lung Cancers Harboring EGFR Exon 20 Insertions

Exon 20 insertions are the third most common family of epidermal growth factor receptor (EGFR) mutations found in non-small-cell lung cancer (NSCLC). Little is known about cancers harboring these mutations aside from their lack of response to EGFR tyrosine kinase inhibitors, impairing the development of effective targeted therapies. NSCLC patients with EGFR genotyping were studied using a mechanism approved by the Institutional Review Board. Cancers with exon 20 insertions were indentified, sequences were characterized, and effectiveness of different treatment regimens was reviewed retrospectively. Clinical characteristics and survival were compared with cancers harboring common EGFR mutations and cancers with wild-type EGFR. One thousand eighty-six patients underwent EGFR genotyping from 2004 to 2012. Twenty seven (2.5%) harbored exon 20 insertions, making up 9.2% of all cancers with documented EGFR mutations. Compared with wild-type cancers, those with exon 20 insertions were more commonly found in never-smokers and Asian patients. Insertion sequences were highly variable, with the most common variant (V769_D770insASV) making up only 22% of cases. Median survival of patients with exon 20 insertions was 16 months, similar to the survival of wild-type cancers and shorter than the survival of cancers with common EGFR mutations. Patients with EGFR exon 20 insertions have similar clinical characteristics to those with common EGFR mutations but a poorer prognosis. The prevalence of this subset of NSCLC is similar to that of other genotype-defined subsets of lung adenocarcinoma (e.g. those with BRAF mutations, HER2 insertions, ROS1 rearrangements) and is a population of interest for trials of new targeted therapies.

Non-Invasive Imaging Provides Spatiotemporal Information on Disease Progression and Response to Therapy in a Murine Model of Multiple Myeloma

BackgroundMultiple myeloma (MM) is a B-cell malignancy, where malignant plasma cells clonally expand in the bone marrow of older people, causing significant morbidity and mortality. Typical clinical symptoms include increased serum calcium levels, renal insufficiency, anemia, and bone lesions. With standard therapies, MM remains incurable; therefore, the development of new drugs or immune cell-based therapies is desirable. To advance the goal of finding a more effective treatment for MM, we aimed to develop a reliable preclinical MM mouse model applying sensitive and reproducible methods for monitoring of tumor growth and metastasis in response to therapy.Material and MethodsA mouse model was created by intravenously injecting bone marrow-homing mouse myeloma cells (MOPC-315.BM) that expressed luciferase into BALB/c wild type mice. The luciferase in the myeloma cells allowed in vivo tracking before and after melphalan treatment with bioluminescence imaging (BLI). Homing of MOPC-315.BM luciferase+ myeloma cells to specific tissues was examined by flow cytometry. Idiotype-specific myeloma protein serum levels were measured by ELISA. In vivo measurements were validated with histopathology.ResultsStrong bone marrow tropism and subsequent dissemination of MOPC-315.BM luciferase+ cells in vivo closely mimicked the human disease. In vivo BLI and later histopathological analysis revealed that 12 days of melphalan treatment slowed tumor progression and reduced MM dissemination compared to untreated controls. MOPC-315.BM luciferase+ cells expressed CXCR4 and high levels of CD44 and α4β1 in vitro which could explain the strong bone marrow tropism. The results showed that MOPC-315.BM cells dynamically regulated homing receptor expression and depended on interactions with surrounding cells.ConclusionsThis study described a novel MM mouse model that facilitated convenient, reliable, and sensitive tracking of myeloma cells with whole body BLI in living animals. This model is highly suitable for monitoring the effects of different treatment regimens.

Small cell lung cancer: effectiveness of different treatment regimens, long-term results and prognosis

Aim. To evaluate the efficacy and safety of different treatment regimens of patients with small cell lung cancer. Methods. Examined were 76 patients, 17 (22.4%) females and 59 (77.6%) males, mean age 62±4.87 years, divided into two groups. The first group consisted of 46 (60.5%) individuals with a generalized form of the disease, the second group consisted of 30 (39.5%) patients with localized cancer. Results. In patients with a localized form of lung cancer the most effective treatment method was a combination of surgical treatment with chemotherapy. In this group in the near-term period noted was a complete regression of the disease, while in the long-term period - a statistically significant improvement of 2- and 3-year survival compared with patients receiving chemotherapy alone. In patients with a generalized form of small cell lung cancer the best immediate and long-term results were observed after chemoradiotherapy compared with chemotherapy alone, which was reflected in statistically significant improvement of parameters of partial remission and stabilization of the disease, as well as improved 1- and 2-year survival. Conclusion. The use of chemotherapy in combination with surgical treatment for localized forms and chemoradiotherapy for generalized forms of small cell lung cancer is characterized by higher indices of treatment efficacy compared to administration of just chemoradiotherapy or chemotherapy, respectively.

PMO-157 HBSAG plasma levels decline helps to predict HBEAG loss but is similar in different NUCLEOS(T)IDE analogues regimens

IntroductionThe kinetics of serum HBsAg (qHBsAg) decline predict response to treatment with pegylated interferon (Peg-IFN) in chronic hepatitis B (CH-B). Whereas nucleos(t)ide analogue (NA) therapy is associated with a sharp...

Effectiveness of different treatment regimens for peri-implantitis

Systematic review conclusion Little reliable evidence exists to indicate the most effective method of treating peri-implantitis. Critical summary assessment The results of this thorough review show that although treatments for peri-implantitis may be effective, not enough evidence exists to recommend one treatment definitively over any other. Evidence quality rating Limited.

One-phase vs 2-phase treatment for developing Class III malocclusion: A comparison of identical twins

Despite the known influence of early treatment on the facial appearance of growing patients with skeletal Class III malocclusion, few comparative reports on the long-term effects of different treatment regimens (1-phase vs 2-phase treatment) have been published. Uncertainty remains regarding the effects of early intervention on jaw growth and its effectiveness and efficiency in the long term. In this case report, we compared the effects of early orthodontic intervention as the first phase of a 2-phase treatment vs 1-phase fixed appliance treatment in identical twins over a period of 11 years. Facial and dental changes were recorded, and cephalometric superimpositions were made at 4 time points. In spite of the different treatment approaches, both patients showed identical dentofacial characteristics in the retention phase. Through this case report, we intended to clarify the benefits of undergoing 1-phase treatment against 2-phase treatment protocols for treating growing skeletal Class III patients.

Weight Beneficial Treatments for Type 2 Diabetes

The close link between type 2 diabetes and excess body weight highlights the need to consider the weight effects of different treatment regimens. We examine the impact of "weight-friendly" type 2 diabetes pharmacotherapies and suggest treatment strategies that mitigate weight gain. Evidence was identified via PubMed search by class and agent and in bibliographies of review articles, with final articles for inclusion selected by author consensus. Substantial evidence confirms the weight benefits of metformin and shows that, of the newer available agents, glucagon-like peptide-1 (GLP-1) agonists and amylin analogs promote weight loss. Dipeptidyl peptidase-4 (DPP-4) inhibitors and bile acid sequestrants are weight-neutral. Liraglutide and exenatide appear to have similar effects on weight; however, recent research suggests a potentially greater effect of liraglutide on glycemic control compared to exenatide, when used as a second-line therapy. Mounting evidence suggests that insulin detemir may provide the most favorable weight benefits of available insulins. Weight-beneficial agents should be considered in patients, particularly obese patients, who fail to reach glycemic targets on metformin therapy. We propose the following treatment choices based on potential weight benefit and blood glucose increment: long-acting GLP-1 agonists (liraglutide), DPP-4 inhibitors, bile acid sequestrants, amylin analogs, and basal insulin for patients with elevated fasting plasma glucose; and short-acting (exenatide) or long-acting GLP-1 agonists, amylin analogs, DPP-4 inhibitors, acarbose, and bile acid sequestrants for patients with elevated postprandial glucose. The weight-sparing effects of insulin detemir, notably in patients with high body mass index, should also be considered when initiating insulin therapy.

Impacto da terapia hormonal sobre o peso corpóreo

to evaluate the effect of hormone replacement therapy (HT) on the weight on perimenopausal women as well as the effect of different treatment regimens on this parameter. a retrospective study of 139 women with menopause for less than 2 years, who were monitored with periodical visits in our department. We compared two groups: women who started HT (n=89) with women who had no hormonal treatment (n=50) and in the two groups, we evaluated the changes in body weight over a 1-year period. In the first group, we assessed the same parameter as a function of different treatment regimens: estrogen alone versus estrogen combined with progestin and standard dose versus low dose. The SPSS® program was used for statistical analysis, with the level of significance set at p<0.05. the groups were similar with respect to demographic and baseline characteristics; weight gain was higher in the untreated group (434 vs 76 g), but the difference observed was not significant (p = 0.406); among HT users, those taking estrogen alone had an increased weight gain compared to women taking estrogen with progestin (775 vs 24 g), although no statistically significant difference was observed and the same applied when comparing the dose initially prescribed (92 vs 49 g). despite the common belief about weight gain associated with HT, the results of the present study seem to contradict this point, with no additional weight gain beyond that normally associated with this period in a woman's life.

Control of Postprandial Glucose Levels with Insulin in Type 2 Diabetes

The importance of maintaining effective glycemic control in patients with type 2 diabetes mellitus (T2DM) is well known. It is increasingly recognized that postprandial hyperglycemia is an important component of the overall glycemic burden, though there is as yet a paucity of data showing that lowering of postprandial plasma glucose (PPG) reduces risk of T2DM complications. The contribution of PPG to overall glycemic control is greatest when glycated hemoglobin (HbA1c) is approximately 7% to 8%. Clinical studies show that targeting PPG can improve glycemic control and long-term prognosis in patients with T2DM. Guidelines for T2DM management now include target levels for PPG as treatment goals. One effective approach to PPG control is achieved using mealtime administration of insulin with a rapid onset of effect and a short duration of action, so that PPG excursions are limited without increased risk of hypoglycemia. Basal-bolus and biphasic insulin regimens achieve good PPG control, even in patients unable to reach glycemic targets with other treatments. Although clinical studies are increasingly including PPG as an endpoint, more interventional studies are needed to investigate the effect of different treatment regimens on PPG and the effect of PPG on clinical outcome. This will facilitate future recommendations for the most effective treatment of T2DM. Postprandial glucose is an important glycemic burden in many patients; routine targeting and regular monitoring has potential to ameliorate the cardiovascular complications of T2DM.

Evaluation of immunosuppressive regimens for immune-mediated haemolytic anaemia: a retrospective study of 42 dogs

Immune-mediated haemolytic anaemia (IMHA) is a severe disease for which evidence is lacking to make informed choices regarding immunosuppressive regimen. The aims of the current study were to determine the effect of different treatment regimens on outcome in affected animals and to identify parameters that may be used as prognostic factors for the disease. The records of dogs presenting to a veterinary hospital in the period 2002 to 2010 for treatment of IMHA were examined and follow-up data were obtained. Statistical tests were performed to establish whether treatment regimen affected outcome and to identify prognostic factors for outcome. Treatment regimen had a significant effect on the outcome (measured as survival of hospitalisation) but there were insufficient subjects to determine the cause of the difference. Serum bilirubin and urea concentrations were found to be significant negative prognostic factors for the outcome of IMHA cases and the concentrations of these parameters were significantly different between animals that survived or died while hospitalised. This study presents the first report of a significant difference in outcome comparing animals treated with immunosuppressive drugs which are in widespread clinical usage. Although possible confounding factors should be considered, these findings could have major consequences for the treatment of IMHA.

Joint modeling of longitudinal data and informative dropout time in the presence of multiple changepoints

In longitudinal studies of patients with the human immunodeficiency virus (HIV), objectives of interest often include modeling of individual-level trajectories of HIV ribonucleic acid (RNA) as a function of time. Such models can be used to predict the effects of different treatment regimens or to classify subjects into subgroups with similar trajectories. Empirical evidence, however, suggests that individual trajectories often possess multiple points of rapid change, which may vary from subject to subject. Additionally, some individuals may end up dropping out of the study and the tendency to drop out may be related to the level of the biomarker. Modeling of individual viral RNA profiles is challenging in the presence of these changes, and currently available methods do not address all the issues such as multiple changes, informative dropout, clustering, etc. in a single model. In this article, we propose a new joint model, where a multiple-changepoint model is proposed for the longitudinal viral RNA response and a proportional hazards model for the time of dropout process. Dirichlet process (DP) priors are used to model the distribution of the individual random effects and error distribution. In addition to robustifying the model against possible misspecifications, the DP leads to a natural clustering of subjects with similar trajectories which can be of importance in itself. Sharing of information among subjects with similar trajectories also results in improved parameter estimation. A fully Bayesian approach for model fitting and prediction is implemented using MCMC procedures on the ACTG 398 clinical trial data. The proposed model is seen to give rise to improved estimates of individual trajectories when compared with a parametric approach.

Effectiveness of different treatment regimens in helicobacter pylori eradication: Ten-year experience of a single institution

We aimed to report the outcomes of different H. pylori eradication regimens used in our institution over the last 10 years. Retrospectively, H. pylori-positive patients who were referred for upper gastrointestinal endoscopy with dyspeptic symptoms and who started eradication treatment and returned for a follow-up visit were included in the study. Subjects were allocated into six groups according to their treatment regimens as follows: Group 1) Proton pump inhibitor, clarithromycin and amoxicillin for 2 weeks; Group 2) Colloidal bismuth subcitrate, metronidazole and tetracycline for 2 weeks; Group 3) ranitidine bismuth citrate, clarithromycin and amoxicillin for 2 weeks; Group 4) Proton pump inhibitor, colloidal bismuth subcitrate, clarithromycin and amoxicillin for 2 weeks; Group 5) Proton pump inhibitor, tetracycline and amoxicillin for 2 weeks; and Group 6) Proton pump inhibitor and amoxicillin for 5 days, followed consecutively by Proton pump inhibitor, clarithromycin and metronidazole for 5 days. A follow-up visit to determine eradication was scheduled a minimum of 6 weeks after completion of the treatment. In this study, 400 patients were included. Eradication rates were 74.7%, 92.3%, 81.2%, 81.5%, 70.5%, and 66.6% in Groups 1-6, respectively. In Group 1, the eradication rate was lower than 80%. In Groups 34, the eradication rate increased to over 80%. The colloidal bismuth subcitrate, metronidazole and tetracycline regimen (Group 2) was the most successful, with a rate of 92.3%. The eradication rate in the consecutive regimen group (Group 6) did not reach the recommended level (higher than 80-85%).

Anxiety, depression and acupuncture: A review of the clinical research

Depression and anxiety together constitute a significant contribution to the global burden of disease. Acupuncture is widely used for treatment of anxiety and depression and use is increasing. The theoretical basis for acupuncture diagnosis and treatment derives from traditional Chinese medicine theory. An alternative approach is used in medical acupuncture which relies more heavily on contemporary neurophysiology and conventional diagnosis. Trials in depression, anxiety disorders and short-term acute anxiety have been conducted but acupuncture interventions employed in trials vary as do the controls against which these are compared. Many trials also suffer from small sample sizes. Consequently, it has not proved possible to accurately assess the effectiveness of acupuncture for these conditions or the relative effectiveness of different treatment regimens. The results of studies showing similar effects of needling at specific and non-specific points have further complicated the interpretation of results. In addition to measuring clinical response, several clinical studies have assessed changes in levels of neurotransmitters and other biological response modifiers in an attempt to elucidate the specific biological actions of acupuncture. The findings offer some preliminary data requiring further investigation.

Investigation of the Effect of Different Treatment Regimens on Blood Acid-Base Balance in Cows with Ketosis

Investigation of the Effect of Different Treatment Regimens on Blood Acid-Base Balance in Cows with Ketosis

Low-intensity ultrasound adjuvant therapy: enhancement of doxorubicin-induced cytotoxicity and the acoustic mechanisms involved.

In this study, the effects of low-intensity pulsed ultrasound (LIU) as an adjuvant to doxorubicin (DOX) treatment was further investigated in comparison to hyperthermia as another widely used adjuvant. The effects were compared with respect to cell killing and apoptosis induction in U937 cells. Human primary liver cancer (PLC) cells were also used to evaluate the effects of the combinations. The use of an echo contrast agent was investigated for further enhancement of cytotoxicity. Finally, the acoustic mechanisms involved were investigated. The effects of different treatment regimens on cell viability were determined using the Trypan blue dye-exclusion test. Apoptosis induction was detected by flow cytometry using fluorescein isothiocyanate-annexin V and propidium iodide staining. The mechanistic study involved electron paramagnetic spin trapping for detecting free radical formation as an indicator of the occurrence of inertial cavitation and spectrophotometry for sucrose hydrolysis as an indicator for noncavitational effects. The combination treatments exerted synergistic effects on cytotoxicity depending on the acoustic conditions used. The use of LIU as an adjuvant to DOX treatment was shown to be superior to the use of hyperthermia as an adjuvant. Moreover, the combination seems to be promising for other cancer types provided that the acoustic conditions are properly selected with respect to drug concentration. The key ultrasound mechanism responsible for the synergism observed was shown to be the production of free radicals by inertial cavitation. Non-cavitational forces were also shown to contribute to the effect. This study is motivating to engage in in vivo research with various cancer types as a step toward clinical applicability and is emphasizing on the importance of developing therapeutic protocols for setting LIU parameters with respect to other therapeutic conditions.