OBJECTIVE: To evaluate the predictive factors of tumor growth in patients with vestibular schwannoma (VS) managed with the wait-and-scan approach.
METHODS: The data of 31 patients diagnosed with intracanalicular VS and followed for > 5 years were retrospectively analyzed. VS was diagnosed according to MRI findings and tumor growth was monitored. Tumor growth was defined as an increase of 2 mm or more in the maximal tumor diameter. The association between the initial tumor size and shape and tumor growth was assessed.
RESULTS: Tumor growth was observed in 16 of 31 patients (51.6%) over a mean follow-up duration of 7.3 years. The initial tumor size was not statistically correlated with tumor growth. However, fusiform or cylindrical tumors exhibited higher growth rates than oval or round tumors. Additionally, a significant correlation was observed between cerebellopontine angle extension and tumor shape.
CONCLUSIONS: In this study, 51.6% of the patients with intracanalicular VS who were managed with the wait-and-scan strategy over a follow-up period of > 5 years showed tumor growth. Tumor shape, especially fusiform or cylindrical shape, was found to be a significant predictor of tumor growth.

OBJECTIVE: To investigate the therapeutic effects of Zeaxanthin (Zea), one of the oxidized xanthophyll carotenoids belonging to the isoprenoids, on inhibiting the angiogenesis and tumor growth of glioblastoma (GBM) via an in vitro and in vivo study.
METHODS: The effects of Zea on the proliferation, adhesion, migration and invasion of human GBM cell lines were detected by cell proliferation assay, cell adhesion assay and Transwell assay. The effect of Zea on angiogenesis was detected by rat aortic ring assay and human umbilical vein endothelial cells (HUVEC) in vitro tube formation assay. The effects of Zea on PARP, Caspase 3 and VEGFR2 phosphorylation as well as VEGFR2\'s downstream signaling pathway were detected by Western blot. The in vivo human GBM xenograft mouse model was employed to study the therapeutic efficacy of Zea.
RESULTS: Zea impaired the proliferation, adhesion, migration and invasion of U87 and U251 cells as well as HUVECs. Rat aortic ring experiments displayed Zea significantly inhibited angiogenesis during VEGF-induced microvascular germination. In vitro and in vivo vascular experiments verified that Zea inhibited VEGF-induced HUVEC proliferation and capillary-like tube formation. Additionally, Zea induced GBM cells apoptosis via increasing the expression of cleaved PARP and Caspase 3. In HUVECs and U251 GBM cells, Zea down-regulated VEGF-induced activation of the VEGFR2 kinase pathway. Meanwhile the expression of p-AKT, p-ERK, p-STAT3 and FAK were all attenuated in U251 cells. Moreover, the effects of Zea on GBM cells proliferation could be blocked by VEGFR2 kinase inhibitor SU5408. These results suggest that Zea may hinder GBM angiogenesis and tumor growth through down-regulating a cascade of oncogenic signaling pathways, both through the inhibition of angiogenesis and the anti-tumor mechanism of a direct cytotoxic effect. Besides, Zea inhibits GBM angiogenesis and tumor growth exemplified through a xenograft mouse model in vivo.
CONCLUSIONS: Zea impairs angiogenesis and tumor growth of GBM both in vitro and in vivo. It can be declared that Zea is a potential valuable anticancer candidate for the future treatment strategy of GBM.

UNASSIGNED: To evaluate the inhibitory effect of ginsenoside Rg3 combined with 5-fluorouracil (5-FU) on tumor angiogenesis and tumor growth in colon cancer in mice.
UNASSIGNED: CT26 mouse model of colon cancer was established and the mice were randomly assigned to the control group, the ginsenoside Rg3 group, the 5-FU group, and the Rg3 combined with 5-FU group. The 5-FU group was injected intraperitoneally at the dose of 20 mg/kg, 0.2 mL/animal, and once a day for 10 days. Treatment for the Rg3 group was given at the dose of 20 mg/kg, 0.2 mL/animal, and once a day for 21 days via gastric gavage. The dose and the mode of treatment for the Rg3+5-FU combination group were the same as those for the 5-FU and the Rg3 group. The control group was intraperitoneally injected with 0.2 mL/d of normal saline for 10 days. The expression of vascular endothelial growth factor (VEGF) and CD31 and the microvascular density (MVD) of the tumor tissues were examined by immunohistochemistry. The blood flow signals and tumor necrosis were examined by color Doppler flow imaging (CDFI). The quality of life, survival rate, tumor volume, tumor mass, and tumor inhibition rate of the mice were monitored.
UNASSIGNED: After 21 days of treatment, the tumor volume and the tumor mass of all treatment groups were significantly decreased compared with those the control group, with the combination treatment group exhibiting the most significant decrease. The tumor inhibition rates of the Rg3 group, the 5-FU group, and the combination group were 29.96%, 68.78%, and 73.42%, respectively. Rg3 treatment alone had inhibitory effect on tumor growth to a certain degree, while 5-FU treatment alone or 5-FU combined with Rg3 had a stronger inhibitory effect on tumor growth. The tumor inhibition rate of the combination group was higher than that of the 5-FU group, but the difference was not statistically significant (P>0.05). Color Doppler ultrasound showed that there were multiple localized and large tumor necrotic areas that were obvious and observable in the Rg3 group and the combination group, and that there were only small tumor necrotic areas in the 5-FU group and the control group. The tumor necrosis rate of the combination group was (55.63±3.12)%, which was significantly higher than those of the other groups (P<0.05). CDFI examination of the blood flow inside of the tumor of the mice showed that the blood flow signals in the combination group were mostly grade 0-Ⅰ, and that the blood flow signals in the control group were the most abundant, being mostly grade Ⅱ-Ⅲ. The abundance of the blood flow signals in the Rg3 and 5-FU groups were between those of the control group and the combination group. Compared with those of the control group, the expression levels of MVD and VEGF in the tumor tissues of the Rg3 group, the 5-FU group, and the combination group were significantly decreased, with the combination group showing the most significant decrease (P<0.05). HE staining results indicated that there was significant tumor necrosis in mice in the control group and that there were more blood vessels. In contrast, in the tumor of the Rg3 group and the 5-FU group, there were fewer blood vessels and necrotic gaps appeared within the tumors. In the combination group, the tumor tissues had the fewest blood vessels and rope-like necrosis was observed. The mice started dying on the 18th day after treatment started, and all the mice in the control group died on the 42nd day. By this time, there were 3, 5, and 7 mice still alive in the Rg3 group, the 5-FU group, and the combination group, respectively, presenting a survival rate of 30%, 50%, and 70%, respectively. All mice in all the groups died on day 60 after treatment started.
UNASSIGNED: Ginsenoside Rg3 combined with 5-FU can significantly inhibit tumor angiogenesis and tumor growth of colon cancer in mice and improve the survival and quality of life of tumor-bearing mice.

Cytochrome P450 (CYP450) enzyme has been shown to be expressed in colorectal cancer (CRC) and its dysregulation is linked to tumor progression and a poor prognosis. Here we investigated the therapeutic potential of targeting CYP450 using lopinavir/ritonavir in CRC. The integrative systems biology method and RNAseq were utilized to investigate the differential levels of genes associated with patients with colorectal cancer. The antiproliferative activity of lopinavir/ritonavir was evaluated in both monolayer and 3-dimensional (3D) models, followed by wound-healing assays. The effectiveness of targeting CYP450 was examined in a mouse model, followed by histopathological analysis, biochemical tests (MDA, SOD, thiol, and CAT), and RT-PCR. The data of dysregulation expressed genes (DEG) revealed 1268 upregulated and 1074 down-regulated genes in CRC. Among the top-score genes and dysregulated pathways, CYPs were detected and associated with poor prognosis of patients with CRC. Inhibition of CYP450 reduced cell proliferation via modulating survivin, Chop, CYP13a, and induction of cell death, as detected by AnnexinV/PI staining. This agent suppressed the migratory behaviors of cells by induction of E-cadherin. Moreover, lopinavir/ritonavir suppressed tumor growth and fibrosis, which correlated with a reduction in SOD/thiol levels and increased MDA levels. Our findings illustrated the therapeutic potential of targeting the CYP450 using lopinavir/ritonavir in colorectal cancer, supporting future investigations on this novel therapeutic approach for the treatment of CRC.

OBJECTIVE: Hepatocellular carcinoma (HCC) is one of the most common types of hepatic carcinoma. The overall prognosis is poor. DAZAP1, a regulator of alternative splicing (AS) events, may participate in tumor growth.
METHODS: We collected 105 HCC patients and tissue samples from the Department of Hepatological Surgery in the Second Affiliated Hospital of Qiqihar Medical University. TCGA datasets were downloaded and operated using the R project. DAZAP1 expressions were examined by quantitative RT-PCR and western blotting. CCK8 assay was used to investigate the cell proliferation, and transwell assay was employed to examine the ability of migration and invasion in vitro. Contrast-enhanced ultrasound (CEUS) was used to evaluate images and parameters of the tumor.
RESULTS: DAZAP1 is highly expressed in the tissue samples of HCC. The peak intensity (PI) and area under the curve (AUC) of the tumor is higher than that of liver parenchyma, and correlated with high DAZAP1 expression. Parameters of CEUS in the tumor are correlated with TNM stage, tumor size, and vascularity. High DAZAP1 expression correlates with a shorter survival time and advanced histologic grade (G3-G4). Bioinformatical analysis revealed that downregulation of DAZAP1 identified differentiated expressed genes (DEGs) involved in the tumor growth process.
CONCLUSIONS: DAZAP1 is highly expressed in hepatic carcinoma and related to the blood flow, and high DAZAP1 expression predicts poor prognosis. DAZAP1 may promote liver carcinoma cell proliferation, migration, and invasion of HEPG2 cells. CEUS parameters are related to the high DAZAP1 expression, and will help to differentiate the HCC tumor.

Few studies have investigated the 1930s hypothesis that reproductive tract infections are risk factors for fibroid development. In our 2017 cross-sectional analysis from the Study of Environment, Lifestyle, and Fibroids (2010-2018), a large Detroit community-based cohort of 23-35 year-old African-American women with ultrasound fibroid screening, we found an inverse association between seropositivity for genital Chlamydia trachomatis (gCT) infection and fibroids. With prospective data from the cohort (standardized ultrasounds every 20 months over 5 years), we examined gCT\'s associations with fibroid incidence (among 1158 women fibroid-free at baseline) and growth. We computed adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for incidence by gCT serostatus using Cox proportional hazards models. GCT\'s influence on growth was assessed by estimating the difference between fibroid size change for seropositive vs. seronegative between successive ultrasounds (1254 growth measures) using a linear mixed model. Growth was scaled to change over 18 months. GCT seropositivity was not associated with fibroid incidence (aHR, 1.0 95% CI: 0.79, 1.29) or growth (4.4%, 95% CI: -5.02, 14.64). The current evidence based on both biomarker gCT data, which can capture the common undiagnosed infections, and prospective ultrasound data for fibroids suggests that Chlamydia is unlikely to increase fibroid risk.

As shown recently, oleic acid (OA) in complex with lactoferrin (LF) causes the death of cancer cells, but no mechanism(s) of that toxicity have been disclosed. In this study, constitutive parameters of the antitumor effect of LF/OA complex were explored. Complex LF/OA was prepared by titrating recombinant human LF with OA. Spectral analysis was used to assess possible structural changes of LF within its complex with OA. Structural features of apo-LF did not change within the complex LF:OA = 1:8, which was toxic for hepatoma 22a cells. Cytotoxicity of the complex LF:OA = 1:8 was tested in cultured hepatoma 22a cells and in fresh erythrocytes. Its anticancer activity was tested in mice carrying hepatoma 22a. In mice injected daily with LF-8OA, the same tumor grew significantly slower. In 20% of animals, the tumors completely resolved. LF alone was less efficient, i.e., the tumor growth index was 0.14 for LF-8OA and 0.63 for LF as compared with 1.0 in the control animals. The results of testing from 48 days after the tumor inoculation showed that the survival rate among LF-8OA-treated animals was 70%, contrary to 0% rate in the control group and among the LF-treated mice. Our data allow us to regard the complex of LF and OA as a promising tool for cancer treatment.

Among the in vivo experimental models, the chick embryo chorioallantoic membrane (CAM) has been routinely used to implant several malignant cell lines or tumor tissues to study their angiogenic and metastatic capability. Since the chick embryo is naturally immunodeficient, the CAM can support the engraftment of tumor cells, and their growth therein can faithfully recapitulate most of the characteristics of the carcinogenic process including: growth, invasion, angiogenesis and colonization of distant tissues. This review article is focused on the discussion of the more recent literature data concerning the use of the CAM to investigate the metastatic process.

Multiple endocrine neoplasia type 1 (MEN1)-related neuroendocrine tumors (NETs) of the lung are mostly indolent, with a good prognosis. Nevertheless, cases of aggressive lung NET do occur, and therefore the management of individual patients is challenging.
To assess tumor growth and the survival of patients with MEN1-related lung NETs at long-term follow-up.
The population-based Dutch MEN1 Study Group database (n = 446) was used to identify lung NETs by histopathological and radiological examinations. Tumor diameter was assessed. Linear mixed models and the Kaplan-Meier method were used for analyzing tumor growth and survival. Molecular analyses were performed on a lung NET showing particularly aggressive behavior.
In 102 patients (22.9% of the total MEN1 cohort), 164 lesions suspected of lung NETs were identified and followed for a median of 6.6 years. Tumor diameter increased 6.0% per year. The overall 15-year survival rate was 78.0% (95% confidence interval: 64.6-94.2%) without lung NET-related death. No prognostic factors for tumor growth or survival could be identified. A somatic c.3127A > G (p.Met1043Val) PIK3CA driver mutation was found in a case of rapid growing lung NET after 6 years of indolent disease, presumably explaining the sudden change in course.
MEN1-related lung NETs are slow growing and have a good prognosis. No accurate risk factors for tumor growth could be identified. Lung NET screening should therefore be based on well-informed, shared decision-making, balancing between the low absolute risk of an aggressive tumor in individuals and the potential harms of frequent thoracic imaging.

The application of local hyperthermia, particularly in conjunction with other treatment strategies (like chemotherapy and radiotherapy) has been known to be a useful means of enhancing tumor treatment outcomes. However, to our knowledge, there has been no mathematical model designed to capture the impact of the combination of hyperthermia and chemotherapies on tumor growth and control. In this study, we propose a nonlinear Partial Differential Equation (PDE) model which describes the tumor response to chemotherapy, and use the model to study the effects of hyperthermia on the response of prototypical tumor to the generic chemotherapeutic agent. Ultrasound energy is delivered to the tumor through High Intensity Focused Ultrasound (HIFU), as a noninvasive technique to elevate the tumor temperature in a controlled manner. The proposed tumor growth model is coupled with the nonlinear density dependent Westervelt and Penne\'s bio-heat equations, used to calculate the net delivered energy and temperature of the tumor and its surrounding normal tissue. The tumor is assumed to be composed of two species: drug-sensitive and drug-resistant. The central assumption underlying our model is that the drug-resistant species is converted to a drug-sensitive type when the tumor temperature is elevated above a certain threshold temperature. The \"in silico\" results obtained, confirm that hyperthermia can result in less aggressive tumor development and emphasize the importance of designing an optimized thermal dose strategy. Furthermore, our results suggest that increasing the length of the on/off cycle of the transducer is an efficient approach to treatment scheduling in the sense of optimizing tumor eradication.