Hepatocellular carcinoma (HCC) is the third most frequent source of deaths associated with cancer after lung cancer in the world despite recent innovative treatment techniques. Liver transplantation, hepatic resection, and percutaneous ablation techniques hold great promise as potentially curative treatments for patients at early stages. Nevertheless, most of the patients are not suitable for these curative treatments due to their advanced disease stages at the time of diagnosis. Food and Drug Administration (FDA) approved tyrosine kinase inhibitor, sorafenib is a standard therapy for advanced-stage HCC patients which extends overall survival for several months. However, its therapeutic efficacy is restricted by adverse events and drug resistance which limits the number of patients benefiting from this systemic chemotherapeutic drug. During the last decade, novel approaches including but not limited to immunotherapies, ablation methods, and chemotherapeutic drugs were proposed to enhance sensitivity to sorafenib, improve therapeutic efficacy, and prohibit adverse events through novel delivery routes, utilization of nanoparticle carriers, and combination with other therapeutic agents. However, studies are still being conducted to optimize the efficiency of sorafenib and reduce its adverse events. In this review paper, we examine research studies evaluating novel delivery methods to reduce drug-related cytotoxicity to improve patient tolerance to sorafenib and its therapeutic efficacy in patients with HCC. Moreover, therapeutic approaches with the synergistic potential to combine with sorafenib are briefly summarized.

Epidermal growth factor receptor (EGFR) is a well-characterized receptor tyrosine kinase that involved in many vital activities in cell development, such as cellular homeostasis, proliferation, division, differentiation and apoptosis. Natural activation of EGFR and the concomitant downstream signaling pathways regulation are substantial to maintain normal cellular functions. In recent studies, EGFR was demonstrated to be a fundamental modulator in the control of skin inflammatory responses. Several dermatologic diseases including psoriasis are related to the anomalous activation of EGFR signaling. It has been proved that the expression and activity of EGFR and its endogenous ligands are overexpressed in the active epidermis lesions of psoriasis. Moreover, the remarkable therapeutic improvement of chronic psoriasis in cancer patients during the treatment of EGFR inhibitors or anti-EGFR monoclonal antibodies are also recorded, suggesting that the EGFR-mediated signaling may conduct a crucial role in the pathophysiology of psoriasis.

Background

Approximately 1/3 of 1990-1 Gulf War veterans developed chronic multisymptom health problems. Implicated exposures bear mechanisms that adversely affect mitochondria. Symptoms emphasize fatigue, cognition and muscle (brain and muscle are aerobically demanding); with protean additional domains affected, compatible with mitochondrial impairment. Recent evidence supports treatments targeting cell bioenergetics (coenzyme10) to benefit Gulf War illness symptoms. However, no evidence has directly documented mitochondrial or bioenergetic impairment in Gulf War illness.

Objective

We sought to objectively assess for mitochondrial dysfunction, examining post-exercise phosphocreatine-recovery time constant (PCr-R) using (31)Phosphorus Magnetic Resonance Spectroscopy ((31)P-MRS), in Gulf War veterans with Gulf War illness compared to matched healthy controls. PCr-R has been described as a "robust and practical" index of mitochondrial status.

Design and participants

Case-control study from 2012-2013. Fourteen community-dwelling Gulf War veterans and matched controls from the San Diego area comprised 7 men meeting CDC and Kansas criteria for Gulf War illness, and 7 non-deployed healthy controls matched 1:1 to cases on age, sex, and ethnicity.

Outcome measure

Calf muscle phosphocreatine was evaluated by (31)P-MRS at rest, through 5 minutes of foot pedal depression exercise, and in recovery, to assess PCr-R. Paired t-tests compared cases to matched controls.

Results

PCr-R was significantly prolonged in Gulf War illness cases vs their matched controls: control values, mean ± SD, 29.0 ± 8.7 seconds; case values 46.1 ± 18.0 seconds; difference 17.1 ± 14.9 seconds; p = 0.023. PCr-R was longer for cases relative to their matched controls for all but one pair; moreover while values clustered under 31 seconds for all but one control, they exceeded 35 seconds (with a spread up to 70 seconds) for all but one case.

Discussion

These data provide the first direct evidence supporting mitochondrial dysfunction in Gulf War illness. Findings merit replication in a larger study and/or corroboration with additional mitochondrial assessment tools.

Background

Approximately 1/3 of 1990-1 Gulf War veterans developed chronic multisymptom health problems. Implicated exposures bear mechanisms that adversely affect mitochondria. Symptoms emphasize fatigue, cognition and muscle (brain and muscle are aerobically demanding); with protean additional domains affected, compatible with mitochondrial impairment. Recent evidence supports treatments targeting cell bioenergetics (coenzyme10) to benefit Gulf War illness symptoms. However, no evidence has directly documented mitochondrial or bioenergetic impairment in Gulf War illness.

Objective

We sought to objectively assess for mitochondrial dysfunction, examining post-exercise phosphocreatine-recovery time constant (PCr-R) using (31)Phosphorus Magnetic Resonance Spectroscopy ((31)P-MRS), in Gulf War veterans with Gulf War illness compared to matched healthy controls. PCr-R has been described as a "robust and practical" index of mitochondrial status.

Design and participants

Case-control study from 2012-2013. Fourteen community-dwelling Gulf War veterans and matched controls from the San Diego area comprised 7 men meeting CDC and Kansas criteria for Gulf War illness, and 7 non-deployed healthy controls matched 1:1 to cases on age, sex, and ethnicity.

Outcome measure

Calf muscle phosphocreatine was evaluated by (31)P-MRS at rest, through 5 minutes of foot pedal depression exercise, and in recovery, to assess PCr-R. Paired t-tests compared cases to matched controls.

Results

PCr-R was significantly prolonged in Gulf War illness cases vs their matched controls: control values, mean ± SD, 29.0 ± 8.7 seconds; case values 46.1 ± 18.0 seconds; difference 17.1 ± 14.9 seconds; p = 0.023. PCr-R was longer for cases relative to their matched controls for all but one pair; moreover while values clustered under 31 seconds for all but one control, they exceeded 35 seconds (with a spread up to 70 seconds) for all but one case.

Discussion

These data provide the first direct evidence supporting mitochondrial dysfunction in Gulf War illness. Findings merit replication in a larger study and/or corroboration with additional mitochondrial assessment tools.

Berberine (BBR), an isoquinoline alkaloid that derived from the Chinese medicinal plant Coptis chinensis, has been identified with multiple pharmacological activities, including regulating glucose and cholesterol levels, anti-obesity effects and anti-diabetic effects. Due to its multiple activities, BBR and its metabolites have drawn great attention in biomedical research and clinical practices. After the recent re-discovery of brown adipose tissue (BAT) in adult humans, stimulating energy-dissipating via BAT activation and white-to-brown adipose tissue conversion have been regarded as potential therapeutic strategies for obesity and diabetes. Recent studies have demonstrated the activities of BBR in the activation of BAT and white-to-brown adipose tissue conversion, showing significant effectiveness in the treatment of diabetes. This review has summarized current studies that focused on the effect of BBR in the treatment of metabolic syndrome, especially in regulating BAT activities. Besides, the potential and molecular mechanisms of BBR in treating other risk factors of metabolic syndrome, including insulin resistance and dyslipidemia, are also reviewed, showing the great potential of BBR in treating the metabolic syndrome systematically.

Hepatocellular carcinoma (HCC) is the most frequent malignancy of the liver, which is considered the fourth leading cause of cancer-related death in the United States. Liver transplant and surgical resection are curative treatments for HCC, but only 10-15% of HCC patients are eligible candidates. The FDA-approved sorafenib is a multi-kinase inhibitor systemic therapy for advanced HCC that extends the overall survival by over 3 months when compared with placebo. Adoptive transfer of Natural Killer (NK) cells holds great promise for clinical cancer treatment. However, only limited clinical benefit has been achieved in cancer patients. Therefore, there is currently considerable interest in development of the combination of sorafenib and NK cells for the treatment of HCC patients. However, the mechanism of how sorafenib affects the function of NK cells remains to be comprehensively clarified. In this paper, we will discuss NK cell-based immunotherapies that are currently under preclinical and clinical investigation and its potential combination with sorafenib for improving the survival of HCC patients.

Osteosarcoma is the most common primary bone malignancy, and surgical resection combined with neoadjuvant chemotherapy is the gold-standard treatment for affected patients. Although the overall survival rates for patients with osteosarcoma currently range from 60% to 70%, outcomes remain disappointing for patients with recurrent, metastatic, or unresectable disease. Irreversible electroporation (IRE) is a novel ablation technique with the potential to elicit an immune response in solid tumors. Dendritic cell (DC)-based tumor vaccines have shown promising therapeutic efficacy in preclinical studies focused on osteosarcoma; however, only limited therapeutic efficacy has been observed in clinical trials. Thus, there is considerable potential therapeutic value in developing combination osteosarcoma treatments that involve IRE and DC-based tumor vaccines. In this review, we discuss recent advances in preclinical and clinical DC-based immunotherapies, as well as potential combinations of DC-based vaccines and IRE, that may improve therapeutic outcomes for patients with osteosarcoma.

To evaluate the value of combining the detection of intratumoral macroscopic fat and hemorrhage in the differentiation of the benign from malignant solid renal masses.Conventional magnetic resonance imaging (MRI), chemical shift (CS)-MRI, and susceptibility-weighted imaging were performed in 152 patients with 152 solid renal masses, including 48 benign and 104 malignant masses all pathologically confirmed. The presence of macroscopic fat detected by CS-MRI and hemorrhage detected by susceptibility-weighted imaging were evaluated in all masses. The rates of macroscopic fat and hemorrhage observed between benign and malignant masses were compared by a χ test. All masses found to contain macroscopic fat with or without hemorrhage were considered to be benign. The remaining masses (without macroscopic fat) found not to contain hemorrhage were considered to be benign. Only those found to contain hemorrhage alone were considered to be malignant. The evaluation indexes for differentiating and forecasting the benign and malignant masses were calculated.Significant differences in the rate of macroscopic fat (observed in 85.42% of benign masses vs. 0% of malignant masses) and hemorrhage (observed in 4.17% of benign masses vs. 95.19% of malignant masses) were measured in the benign and malignant groups (P < 0.005, for both). The 41 masses containing macroscopic fat with or without hemorrhage and 11 masses containing neither macroscopic fat nor hemorrhage were considered to be benign. The 100 masses containing no macroscopic fat and only hemorrhage were considered to be malignant. By combining the results for the macroscopic fat and hemorrhage, the accuracy, sensitivity, and specificity in the differential diagnosis of the benign and malignant masses were 96.05%, 95.19%, and 97.92%, respectively, and the accuracy and error rate of forecasting the benign and malignant masses were 95.39% and 4.61%, respectively.Combining the detection intratumoral macroscopic fat and hemorrhage can be used to differentiate the benign from malignant solid renal masses.

Background

There are inconsistent interpretations of the interrelationship of adiposity, anthropometric indices, and blood pressure (BP) in hypertensive patients. Additionally, whether these relationships differ between sexes is unknown. We aimed to elucidate the associations of adiposity indices measured using quantitative computed tomography (QCT) with BP and hypertension and to determine the effect of sex on the interrelationship of these parameters in a Chinese population.

Methods

Abdominal adipose fat, including the visceral adipose tissue (VAT) area and subcutaneous adipose tissue (SAT) area, was measured by QCT in 1488 patients (514 men, 974 women). Body mass index (BMI), waist circumference (WC), hip circumference (HC), and systolic (SBP) and diastolic BP (DBP) were measured. Pearson correlation coefficients, multivariate analyses, and receiver operating characteristic (ROC) curves were used to assess the relationship and potential of adiposity indices to BP and risk of hypertension within sex groups.

Results

Men had significantly greater VAT area but less SAT area than women in hypertensive group. VAT, SAT, and WC were more highly correlated with SBP in men than in women. After controlling for body weight, height, and age, VAT area and WC were positively associated with SBP (VAT: β = 0.309, p < 0.001; WC: β = 0.148, p = 0.001) and DBP (VAT: β = 0.099, p = 0.034; WC: β = 0.198, p = 0.001) in women. VAT area was positively associated with SBP (β = 0.444, p < 0.001) and DBP (β = 0.146, p = 0.021) in men. WC had a significant correlation with an increased risk of hypertension in women but a borderline association in men (p = 0.059) when adjusted for VAT area and SAT area.

Conclusions

The association of abdominal adiposity with hypertension differs qualitatively by sex. WC may be an important determinant of hypertension and may be used for risk stratification for hypertension among Chinese individuals.

To improve the efficacy of gemcitabine (GEM) for the treatment of advanced pancreatic cancer via local hyperthermia potentiated via a multi-functional nanoplatform permitting both in vivo heating and drug delivery is the goal of this study. Here, a chemohyperthermia approach to synergistically achieve high intra-tumoral drug concentrations, while permitting concurrent hyperthermia for more effective tumor cell kill and growth inhibition, is proposed. Drug delivery and hyperthermia are achieved using a hydroxypropyl cellulose (HPC)-grafted porous magnetic drug carrier that is MRI visible to permit in vivo visualization of the biodistribution. These synthesized magnetic drug carriers produce strong T2 -weighted image contrast and permit efficient heating using low-magnetic-field intensities. The thermomechanical response of HPC permits triggered GEM release confirmed during in vitro drug release studies. During in vitro studies, pancreatic cancer cell growth is significantly inhibited (≈82% reduction) with chemohyperthermia compared to chemotherapy or hyperthermia alone. Using PANC-1 xenografts in nude mice, the delivery of injected GEM-loaded magnetic carriers (GEM-magnetic carriers) is visualized with both MRI and fluorescent imaging techniques. Chemohyperthermia with intra-tumoral injections of GEM-magnetic carriers (followed by heating) results in significant increases in apoptotic cell death compared to tumors treated with GEM-magnetic carriers injections alone. Chemohyperthermia with GEM-magnetic carriers offers the potential to significantly improve the therapeutic efficacy of GEM for the treatment of pancreatic cancer. In vivo delivery confirmation with non-invasive imaging techniques could permit patient-specific adjustments therapeutic regimens for improve longitudinal outcomes.