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This phase II randomized clinical trial aimed to assess the efficacy and toxicity of Endostar, an antiangiogenesis inhibitor, combined with concurrent chemoradiotherapy (CCRT) for locally advanced cervical cancer (LACC). Patients with LACC were randomly assigned to either CCRT plus Endostar (CCRT+E arm) or CCRT alone (CCRT arm). All patients received pelvic intensity-modulated radiation therapy (IMRT) and brachytherapy. Weekly cisplatin was administered concurrently with IMRT. Patients in the CCRT+E arm also received concurrent Endostar every 3 weeks for two cycles. The primary endpoint was progression-free survival (PFS) and acute toxicities. The exploratory endpoint was the impact of vascular endothelial growth factor receptor-2 (VEGFR2) expression on long-term survival. A total of 116 patients were enrolled. Patients in the CCRT+E arm and in the CCRT arm had similar acute and late toxicity profile. The 1- and 2-year PFS were 91.4% versus 82.1% and 80.8% versus 63.5% (p=0.091), respectively. The 1- and 2-year distance metastasis-free survival (DMFS) were 92.7% versus 81.1% and 86.0% versus 65.1% (p=0.031), respectively. Patients with positive VEGFR2 expression had significant longer PFS and overall survival (OS) compared with those with negative VEGFR2 expression. Patients in the CCRT+E arm had significantly longer PFS, OS, and DMFS than those in the CCRT arm when VEGFR2 expression was positive. In conclusion, CCRT plus Endostar significantly improved DMFS but not PFS over CCRT alone. The addition of Endostar could significantly improve survival for patients with positive VEGFR2 expression.

Significant number of literatures has demonstrated the antiproliferative effect of Zerumbone and its role as anti-angiogenesis. The aims of this systematic review were to assess the anti-cancer effects of Zerumbone and the role of its antiangiogenic properties in treating cancer. Relevant articles were selected based on specific inclusion criteria. Articles chosen for this systematic review were between January 2008 and December 2018. Relevant articles were identified through an extensive search in Science Direct, PubMed, Google Scholar and Scopus. The literature searches of the electronic databases combined the following key words: anti-angiogenic, anticancer, Zerumbone and Zingiber zerumbet. Studies chosen for this review includes the following designs in vitro, in vivo and ex vivo. The initial literature search obtained a total of 352 related records and the final number of studies that met the inclusion criteria in the current review was 43 studies. In vitro studies were the commonest study design. Evidently, Zerumbone demonstrate a potential antiproliferative and antiangiogenic. The antiproliferative activities of Zerumbone was shown to induce by different signalling pathway. Zerumbone through its antiangiogenic effect play a great role in reducing invasion and metastasis. Some selected studies on Zerumbone were found to plague with limitation such as lack of toxic threshold value which may be needed for the clinical trials on this compound.

Vessel co-option is an alternative strategy by which tumour cells vascularize and gain access to nutrients to support tumour growth, survival and metastasis. In vessel co-option, the cancer cells move towards the pre-existing vasculature and hijack them. Vessel co-option is adopted by a wide range of human tumours including colorectal cancer liver metastases (CRCLM) and is responsible for the effectiveness of treatment in CRCLM. Furthermore, vessel co-option is an intrinsic feature and an acquired mechanism of resistance to anti-angiogenic treatment. In this review, we describe the microenvironment, the molecular players, discovered thus far of co-opting CRCLM lesions and propose a theoretical model. We also highlight key unanswered questions that are critical to improving our understanding of CRCLM vessel co-option and for the development of effective approaches for the treatment of co-opting tumours.

Cancer pain management is mostly done by opioids; however, they have further pharmacological effects apart from analgesia including angiogenesis. In this study, peripherally acting ligands of µ opi...

Angiogenesis plays an important role in tumour progression. However, anti‐angiogenesis therapy of inhibiting pro‐angiogenic factors failed to meet expectations in certain types of tumour in clinical trials. Recent studies reveal that tumour‐derived extracellular vesicles (EVs) are essential in tumour angiogenesis and anti‐angiogenesis drug resistance. This function has most commonly been attributed to EV contents including proteins and non‐coding RNAs. Here, we summarize the recent findings of tumour‐derived EV contents associated with regulating angiogenesis and illustrate the underlying mechanisms. In addition, the roles of EVs in tumour microenvironmental cells are also illustrated with a focus on how EVs participate in cell‐cell communication, contributing to tumour‐mediated angiogenesis. It will help offer new perspectives on developing targets of anti‐angiogenesis drugs and improve the efficacy of anti‐angiogenesis therapies based on tumour‐derived EVs.

A living therapeutic system based on attenuated Salmonella was developed via metabolic engineering using an aggregation-induced emission (AIE) photosensitizer MA. The engineered bacteria could localize in the tumor tissues and continue to colonize and express exogenous genes. Under light irradiation, the encoded VEGFR2 gene was released and expressed in tumor tissues, which can suppress angiogenesis induced by a T cell-mediated autoimmune response and inhibit tumor growth.

Immune checkpoint inhibition (ICI) has proved successful for selected tumors and a subpopulation of patients. The human monoclonal IgG1 antibody (mAB) avelumab capable of mediating antibody-dependent cytotoxicity (ADCC) lysis is directed to programmed death ligand-1 (PD-L1) of tumor cells and is tested in trials aiming to improve ICI in combination with chemotherapeutic drugs.This article presents an overview of the current trials to enhance ICI regimens using avelumab in combination with chemotherapeutics, antiangiogenetic drugs, and immunomodulators. Predictive factors for this kind of immunochemotherapy are discussed.Clinical data demonstrate that avelumab shows efficacy in cancer patients against Merkel cell carcinoma (MCC), renal cell carcinoma (RCC), and urothelial cancers as single agent. Furthermore, avelumab in combination with axitinib in RCC increases survival and exhibits activity in combination with docetaxel in urothelial carcinoma. However, several other immunochemotherapy trials for ovarian cancer, gastric cancer, and non-small lung cancer (NSCLC) showed no activity due to factors disfavoring administration of immunotherapy combos.

Angiogenesis is involved in the proliferation and metastasis of solid tumours; hence, it is an attractive therapeutic target. However, most patients who undergo anti-angiogenic drug treatment do no...

Background Anti-angiogenic drugs have become a research hotspot in recent years. However, dynamically observing their therapeutic effect at different time points during treatment is a clinical problem. Purpose To explore the feasibility of the quantitative parameters of spectral computed tomography (CT) in evaluating the anti-angiogenic effect of bevacizumab on rat C6 glioma. Material and Methods Twenty-six male Sprague-Dawley rats were used to establish the C6 glioma model. The rats were randomly divided into the experimental group (n = 13) and control group (n = 13). The experimental group was intraperitoneally injected with 0.2 µL/g bevacizumab every day, whereas the control group was injected with the same dose of normal saline every day for one week. Spectral CT scanning was performed on the 4th and 8th days after treatment; meanwhile, the brain tissues were collected by heart perfusion for H&E staining, and VEGF and HIF-1α immunohistochemical staining. Results On the 4th and 8th days, significant differences in the 70-keV single-energy CT value, slope of the energy spectrum curve, and iodine concentration were found between the experimental group and the control group. Correlation analysis between immunohistochemistry and quantitative parameters of spectral CT showed that the single energy CT value of 70 keV, slope of the energy spectrum curve, and concentration of iodine were positively correlated with VEGF and HIF-1α at different time points in the experimental group and the control group. Conclusion Spectral CT multi-parameter imaging can be employed as a new method to evaluate the anti-angiogenic effect of bevacizumab on rat C6 glioma.

The role of angiogeneses during the growth and progression of tumors is well documented. Likewise, a balance is generally maintained between the cellular proliferation and the apoptosis, therefore, the tumors can persist for years in a dormant phase. During the past few years, many hypotheses have been proposed relating to the importance of tumor angiogenesis for the development and spread of tumors and preventive or therapeutic capacity of angiogenesis inhibitors as a potential target for controlling the growth of cancerous tissue. The antiangiogenic based therapeutic approaches are considered as the most promising method for the control of tumors, as this therapeutic approach is less likely to attain the drug resistance. Further, the tumor vasculature is an important prognostic marker that can independently predict the pathological stages as well as the metastatic potential of tumors. Various biologically active phytochemicals have been extracted from the dietary sources and the plants that have engaged the scientist and pharmaceutical industries around the globe. The antioxidant, antiinflammatory, anti-proliferative and anti-angiogenic potential of these bioactive phytochemicals is evident from the in vitro studies using cell lines and investigations involving the animal models..The present review is focused on the promising role of anti-angiogenesis-based therapies for the management of tumors and the recent developments relating to the interplay of phytochemicals and angiogenesis for the suppression of tumor cells.

Aims: This study was to analyze the association among ES, VEGF, Microvessel Density (MVD), clinicopathologic characteristics, angiogenesis and prognosis of OSCC. Methods: Eight normal samples of oral epithelia and 52 Oral Squamous Cell Carcinoma (OSCC) samples were analyzed by immunohistochemical evaluation to study the expression and significance of Endostatin (ES) and Vascular Endothelial Growth Factor (VEGF) during the development of OSCC. Results: Statistically significant differences were found as p

This study was conducted to determine the antitumor effects and ability of an anlotinib (AL) hydrogel (AL–HA–Tyr) to reduce toxicity in a mouse model of Lewis lung cancer (LLC). We constructed a drug carrier system for AL, verified its effectiveness and systemic safety, and provided a preliminary experimental foundation for clinical carrier transformation. AL–HA–Tyr was prepared by encapsulating AL with hyaluronic acid–tyramine (HA–Tyr) conjugates. Colony and tube formation assays showed that AL–HA–Tyr restrained the proliferation of human umbilical vein endothelial cells (HUVECs) and LLC cells, respectively, in vitro, and that AL exerted significant anti-angiogenesis and anti-tumor effects. The invasion and migration of HUVECs and LLC cells were efficiently suppressed by AL according to transwell assays. HUVEC and LLC cell-cycle and apoptosis analysis clarified the direct anti-tumor effects of AL–HA–Tyr. Mice engrafted with LLC cells in vivo were administered oral saline, oral AL, or an intratumoral injection of HA–Tyr or AL–HA–Tyr. The results showed that AL–HA–Tyr obviously reduced visceral toxicity and decreased Ki67 and VEGF-A expression in tumor cells compared with AL. Furthermore, AL–HA–Tyr significantly prolonged the survival of tumor-bearing mice. Overall, AL–HA–Tyr enhanced antitumor effects and reduced toxicity in the LLC model. It provided a foundation for the clinical transformation of drug carrier systems.

Background Surgery-based treatment is the standard method for the early-stage soft tissue sarcoma (STS) with relatively good clinical outcome. However, the recurrence and metastasis decrease the survival of STS, regardless of surgery, radiotherapy, and chemotherapy. On the other hand, anti-angiogenesis treatments for STS have been clinically applied in recent years. To evaluate the safety and efficacy of anti-angiogenesis medicines for the treatment of advanced STS, we conducted a meta-analysis. Methods We systematically searched PubMed, Web of Science, Cochrane Library, Excerpta Medica Database, and China National Knowledge Infrastructure from inception to September 5, 2019. And finally, nine studies with 1,230 patients were included after rigorous screening. The endpoints included objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and adverse reactions (AEs). And we analyzed them with the risk ratio (RR) or the hazard ratio (HR). Moreover, heterogeneity and sensitivity were also analyzed. Results The pooled data showed that anti-angiogenesis medicines significantly benefited ORR [risk ratio (RR) =2.16, 95% CI: 1.47–3.17, P

The IMpower150 trial showed significant improvements in progression-free and overall survival with atezolizumab plus bevacizumab plus carboplatin plus paclitaxel (ABCP) versus the standard-of-care bevacizumab plus carboplatin plus paclitaxel (BCP) in chemotherapy-naive patients with non-squamous non-small-cell lung cancer. Here, we report the efficacy of ABCP or atezolizumab plus carboplatin plus paclitaxel (ACP) versus BCP in key patient subgroups.IMpower150 was a randomised, open-label, phase 3 study done at 240 academic medical centres and community oncology practices across 26 countries worldwide. Patients with chemotherapy-naive metastatic non-small-cell lung cancer were randomly assigned (1:1:1) to receive ABCP, ACP, or BCP every three weeks. The co-primary endpoints were overall survival and investigator-assessed progression-free survival in intention-to-treat wild-type patients (patients with epidermal growth factor receptor [EGFR] or anaplastic lymphoma kinase [ALK] genetic alterations were excluded). Efficacy was assessed in key subgroups within the intention-to-treat population, including patients with EGFR mutations (both sensitising and non-sensitising; EGFR-positive) previously treated with one or more tyrosine kinase inhibitors and patients with baseline liver metastases. Overall survival in the intention-to-treat population was included among secondary efficacy endpoints. Exploratory endpoints included the proportion of patients achieving an objective response in the intention-to-treat population, including EGFR-positive patients and patients with baseline liver metastases. Data are reported as per the Jan 22, 2018, data cutoff date, at which the number of coprimary prespecified overall survival events was met in the ABCP versus BCP groups. This trial is registered with ClinicalTrials.gov, number NCT02366143, and is ongoing.Between March 31, 2015, and Dec 30, 2016, 1202 patients were enrolled. 400 patients were randomly assigned to ABCP, 402 to ACP, and 400 to BCP. In EGFR-positive patients (124 of 1202), median overall survival was not estimable (NE; 95% CI 17·0-NE) with ABCP (34 of 400) and 18·7 months (95% CI 13·4-NE) with BCP (45 of 400; hazard ratio [HR] 0·61 [95% CI 0·29-1·28]). Improved overall survival with ABCP versus BCP was observed in patients with sensitising EGFR mutations (median overall survival NE [95% CI NE-NE] with ABCP [26 of 400] vs 17·5 months [95% CI 11·7-NE] with BCP [32 of 400]; HR 0·31 [95% CI 0·11-0·83]) and in the intention-to-treat population (19·8 months [17·4-24·2] vs 14·9 months [13·4-17·1]; HR 0·76 [0·63-0·93]). Improved median overall survival with ABCP versus BCP was seen in patients with baseline liver metastases (13·3 months [11·6-NE] with ABCP [52 of 400] vs 9·4 months [7·9-11·7] with BCP [57 of 400]; HR 0·52 [0·33-0·82]). Median overall survival was 21·4 months (95% CI 13·8-NE) with ACP versus 18·7 months (95% CI 13·4-NE) with BCP in EGFR-positive patients (HR 0·93 [95% CI 0·51-1·68]). No overall survival benefit was seen with ACP versus BCP in patients with sensitising EGFR mutations (HR 0·90 [95% CI 0·47-1·74]), in the intention-to-treat population (HR 0·85 [0·71-1·03]), or in patients with baseline liver metastases (HR 0·87 [0·57-1·32]). In the intention-to-treat safety-evaluable population, grade 3-4 treatment-related events occurred in 223 (57%) patients in the ABCP group, in 172 (43%) in the ACP group, and in 191 (49%) in the BCP group; 11 (3%) grade 5 adverse events occurred in the ABCP group, as did four (1%) in the ACP group, and nine (2%) in the BCP group.Improved survival was noted for patients treated with ABCP compared with those given BCP in the intention-to-treat population, and in patients with baseline liver metastases. The overall survival signal in the subgroup of patients with EGFR sensitising mutations warrants further study.F. Hoffmann-La Roche, Genentech.

Seven new clerodane diterpenoids, crassifolins Q−W (1–7), along with five known analogues (8–12), were isolated from the roots of Croton crassifolius. Their structures were identified by comprehensive spectroscopic analysis (UV, IR, NMR, and HR-ESI-MS), and their absolute configurations were determined by ECD spectra and X-ray crystallography. The activities of compounds 1–5 against inflammatory cytokines IL-6 and TNF-α levels on LPS-induced RAW 264.7 macrophages were assessed, and compound 5 showed the most significant activity with the secretion levels of IL-6 and TNF-α at 32.78 and 12.53%, respectively. Moreover, compounds 1–5 were screened for their anti-angiogenesis using a human umbilical vein endothelial cells in vitro mode; the results showed all of them exhibited obvious anti-angiogenesis activities, in particular, compound 5 showed the strongest anti-angiogenesis effect in the range of 6.25–50 μM.

The present study focused to synthesize the silver oxide nanoparticles (AgONPs) from endophytic fungus, as the strain eventually possess the medicinal property acquired from the medicinal tree, Aegle marmelos. About 35 pigmented endophytic fungi were isolated, screened for antagonistic activity against 12 clinical human pathogens and antioxidant activity through DPPH radical scavenging assay; among the isolates, FC36AY1 explored the highest activity. The endophytic fungus was identified as Aspergillus terreus FC36AY1 through microscopic and Internal Transcribed Spacer (ITS) 1, ITS 4 and 18S rRNA amplification. The AgONPs were synthesized from the strain FC36AY1 and characterized for its confirmation, functional groups, nanostructures with unit cell dimensions, size and shape, presence of elements through UV-Vis spectrophotometry, FT-IR, X-Ray Diffraction, Scanning Electron Microscopic with EDX analysis. The myco-generated AgONPs manifested their antimicrobial and antioxidant properties with maximum activity at minimum concentration. Moreover, the inhibition of angiogenesis by the AgONPs in Hen’s Egg Test on the Chorio-Allantoic Membrane analysis evinced significant bioactivity at least concentration. Thus the results of this investigation revealed that this bioactive fungal mediated AgONPs can be exploited as potential in biomedical applications.

Clear cell meningioma (CCM), an unusual subtype of World Health Organization (WHO) grade II meningioma, represents only 0.2– 0.8% of meningiomas. Spinal CCMs are even rarer with unique clinical features: more common in younger patients; more likely to appear in lumbar spine; high recurrence rate. Although surgery and radiotherapy are the most common treatment for primary tumors and disease recurrence, there are lack of treatment options for recurrent or metastasis disease. It is urgent need to explore new effective treatment method. In our case, we firstly reported a rare spinal CCM patient with PD-L1 positive and multiple metastases benefiting from PD-1 inhibitor plus anti- angiogenesis therapy. This treatment program is effective, safe, and has a strong therapeutic reference value, which provides promising treatment options and the direction of future clinical trials for spinal CCMs.

Background We previously found that (via inhibition of the VEGF/VEGFR signaling pathway) ckgroundSevacizumab (Sev), an anti-VEGF monoclonal antibody, was proven to have a superior inhibitory effect than bevacizumab (Bev) on the growth of hepatocellular carcinoma (HCC) cells. This study aimed to explore the anti-proliferation and anti-angiogenic effects of Sev on HCC cells in combination with oxaliplatin (OXA) or 5-fluorouracil (5-Fu). Methods In vitro HCC/endothelial cell growth in different concentration drug was analyzed by MTT assay, DAPI and flow cytometry assay. Cell scratch test, transwell assay, tube formation assay, zebrafish assay, and CAM assay were used to investigate anti-angiogenesis effect of drugs. VEGF mRNA relative expression changes of zebrafish embryos were detected by RT-PCR.A fluorescence imaging system was applied to observe the growth of transplantation tumor and blood vessels in HCC mouse xenografts. Tissue H-E staining and TEM detection were used to detect the tumor cell apoptosis. MVD was detected by immunohistochemical analysis of CD31. ELISA and western-blots were used to detect the cell VEGF/VEGFR pathway and its downstream target activity both in vitro and in vivo. Results In vitro results showed that the combination of Sev with OXA/5-Fu can synergistically inhibit the proliferation of HCC and endothelial cells. Compared with the corresponding monotherapy group, combination therapy showed a stronger effect on inducing apoptosis and cell cycle arrest. In vivo findings revealed that Sev in combination with chemotherapy can synergistically inhibit tumor growth by inducing cell apoptosis in nude mice with HCC xenografts. In addition, the wound healing and transwell migration assays demonstrated that Sev can inhibit the migration of endothelial cell lines in combination with chemotherapy. In vitro tube formation test, zebrafish and chicken embryonic-angiogenic assay, immunohistochemistry, and in vivo fluorescence imaging consistently verified that Sev and OXA/5-Fu can synergistically inhibit the growth of blood vessels, and the underlying mechanism may be associated with inhibition of the VEGF/VEGFR signaling pathway. Conclusions The combination of Sev and chemotherapy is associated with the inhibition of HCC growth and tumor angiogenesis, which may provide a significant biological rationale for evaluating the efficacy of Sev and OXA/5-Fu combination therapy on HCC.

Both anti-angiogenesis and immunotherapy are well-established therapeutic options in solid tumors. Here, we review the rationale as well as clinical evidence of combining these two approaches. There is strong rationale and substantial preclinical and clinical evidence that anti-angiogenesis plays a pivotal role in overcoming immunotherapy resistance. The combination of an anti-angiogenic agent and a checkpoint inhibitor offers a more robust treatment option in many clinical trials in a wide variety of solid tumor types. Combination of anti-angiogenesis and immunotherapy has emerged as a standard of care in some tumor types and the indication is expected to expand to more tumor types in the years to come.

Interleukins (ILs) are secreted by leukocytes and macrophages and are involved in communication amongst leukocytes regulating numerous biological processes and immune responses. This review article analyzes the role played by ILs in the regulation of angiogenesis and anti-angiogenesis in both solid and hematological tumors.

Angiogenesis is a critical step in the progression of almost all human malignancies and some other life-threatening diseases. Anti-angiogenic therapy is a novel and effective approach for treatment of angiogenesis-dependent diseases such as cancer, diabetic retinopathy, and age-related macular degeneration. In this article, we will review the main strategies developed for anti-angiogenic therapies beside their clinical applications, the major challenges, and the latest advances in the development of anti-angiogenesis-based targeted therapies.

Over the last decade, new therapeutics in the form of anti-angiogenic treatment, synthetic lethality, and checkpoint inhibition have offered new options for the treatment of ovarian cancer. This review summarizes studies related to these treatment modalities and additionally novel combinations that offer a veritable therapeutic matrix for clinicians to choose from.

In renal cancer emerging treatment options are becoming available and there is a strong need to combine therapies to reformulate and adjourn clinical practice. We here highlight and discuss the need to take advantage of the common immune targets to design combined strategies to increase clinical responses.

A major problem associated with cancer treatment is resistance-prone chemotherapeutic drugs. An increasing number of studies have documented that the occurrence of resistance tends to be associated with abnormal blood vessels. In 2001, Jain proposed the vascular normalization theory, which was recently applied to the drug-resistant treatment of tumors in the clinic. Through the intervention of angiogenesis inhibitors, remodeling the structure and function of abnormal vessels can maximize the efficacy of chemotherapeutic drugs. In this review, we systematically describe the occurrence and progress of tumor angiogenesis, as well as the pathological characteristics of tumor blood vessels. Moreover, druggable targets for vascular normalization and the development of related inhibitors are also outlined.

Both anti-angiogenesis and gene therapy involve complex processes depending on non-point parameters belonging to a space of values. To successfully overcome the challenges involved in their therapeutic approaches, there is a need to analyze the sensitivity of these parameters. In this paper, a new mathematical model that combines immune system stimulations, inflammatory processes associated with tumor development, and gene therapy aimed at enhancing the efficacy of both treatments are explored. Using the global sensitivity methods of Sobol and Morris, the most important parameters are estimated. Estimation of the sensitivity variance revealed a strong interdependence between the parameters. Also, determinations of the conditions for effective therapy lead to a target of reducing the cancer cell numbers by at least 50 % . This opened the way for delimiting the parameter spaces making it possible to reach the treatment target in addition to enhancing the estimation of the minimum time of remission. The combination of therapies and sensitivity analysis have demonstrated the robustness of therapy success.

Background: We recently reported the results of a phase II clinical trial that the combinational use of camrelizumab plus apatinib induced an objective response rate (ORR) at 43.3% in advanced triple-negative breast cancer (TNBC) patients. This study presents the analysis of potential tumor and blood biomarkers for the patients responded to the combinational therapy. Methods: Stromal tumor-infiltrating lymphocytes (TILs), CD8+ T cells and the protein expression of programmed death protein 1 (PD-1) and PD-L1 were evaluated in tumor samples collected before and after the treatment. Peripheral blood samples were collected before treatment, 2-weeks and 8-weeks after treatment. 59 cytokines/chemokines, growth factors, or checkpoint-related proteins, blood immune cell subpopulations were analyzed in the blood samples. The correlation between biomarkers and clinical outcomes including ORR, progression-free survival (PFS), and overall survival (OS) was analyzed. Results: Upon database lock, the ORR of 28 evaluable patients was 46.4%. An increase of tumor-infiltrating CD8+ T cells more than 15% during therapy was significantly associated with higher ORR (P=0.040). Patients with lower baseline plasma levels of HGF or IL-8 were more likely to respond to the combinational treatment (P=0.005 or 0.001, respectively), and showed a longer PFS and OS (HGF: PPFSPOSPPFSPOS=0.009). Patients with a decrease of IL-8, or an increase of TIM-3 or CD152 during treatment responded more to the treatment (P=0.008, 0.040, or 0.014, respectively). Responders had a higher baseline CD4+ T cells and B cell proportions in blood than non-responders (P=0.002 and 0.030 respectively). Moreover, patients with higher baseline CD4+ T cells or B cells proportions in blood showed a longer PFS (PP=0.030) respectively. Conclusion: Higher baseline TILs or a greater increase of tumor-infiltrating CD8+ T cells during therapy, lower baseline plasma HGF/IL-8, a decrease of plasma IL-8, an increase of plasma TIM-3/CD152 during therapy, higher baseline CD4+ T cells or B cells proportion in blood are potential biomarkers for the combinational anti-angiogenesis and immunotherapy in advanced TNBC patients.

Angiogenesis is an important process in tumor growth. Because it is a process that allows the tumor to receive enough nutrients. Anti-angiogenesis therapy is one of the safe tumor treatment processes. It will demolish the angiogenic factors, resulting in tumor lack of the nutrient. The purposes of this study were to develop the new diffusion of nutrient models with tumor treatments to explain the nutrient concentration in each phase and analyze the growth. The simulation results indicate that in the treatment, the effectiveness of the inhibitor affects the concentration, tumor size and time to phase changes. In which the trend of concentration in each phase is different.

Angiogenesis is required in cancer, including gynecological cancers, for the growth of primary tumors and secondary metastases. Development of anti-angiogenesis therapy in gynecological cancers and improvement of its efficacy have been a major focus of fundamental and clinical research. However, survival benefits of current anti-angiogenic agents, such as bevacizumab, in patients with gynecological cancer, are modest. Therefore, a better understanding of angiogenesis and the tumor microenvironment in gynecological cancers is urgently needed to develop more effective anti-angiogenic therapies, either or not in combination with other therapeutic approaches. We describe the molecular aspects of (tumor) blood vessel formation and the tumor microenvironment and provide an extensive clinical overview of current anti-angiogenic therapies for gynecological cancers. We discuss the different phenotypes of angiogenic endothelial cells as potential therapeutic targets, strategies aimed at intervention in their metabolism, and approaches targeting their (inflammatory) tumor microenvironment. ispartof: BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER vol:1875 issue:1 ispartof: location:Netherlands status: published

Aim: This research investigated the therapeutic effect of an allogeneic mouse brain microvascular endothelial cell vaccine on lung cancer and further elucidated its potential anti-angiogenic mechanism. Materials & methods: The immune effect of the allogeneic bEnd.3 vaccine and DC vaccine loaded with bEnd.3 antigen on the subcutaneous transplantation of Lewis lung cancer (LLC) was assessed by ELISA, the CCK test and the CTL killing test. The mechanism was preliminarily revealed by immunohistochemistry and immunoblot analysis. Results: This study revealed that tumor volume was decreased (p .05). Importantly, tumor volume and survival of the T lymphocyte therapeutic group were decreased and prolonged (p

Although decision making strategy based on clinico-histopathological criteria is well established, renal cell carcinoma (RCC) represents a spectrum of biological ecosystems characterized by distinct genetic and molecular alterations, diverse clinical courses and potential specific therapeutic vulnerabilities. Given the plethora of drugs available, the subtype-tailored treatment to RCC subtype holds the potential to improve patient outcome, shrinking treatment-related morbidity and cost. The emerging knowledge of the molecular taxonomy of RCC is evolving, whilst the antiangiogenic and immunotherapy landscape maintained and reinforced their potential. Although several prognostic factors of survival in patients with RCC have been described, no reliable predictive biomarkers of treatment individual sensitivity or resistance have been identified. In this review, we summarize the available evidence able to prompt more precise and individualized patient selection in well-designed clinical trials, covering the unmet need of medical choices in the era of next-generation anti-angiogenesis and immunotherapy.

The authors have requested that this preprint be removed from Research Square.

Anti-angiogenic therapy is a novel treatment approach for cancer that aims at preventing a tumor from developing its own blood supply system that it needs for growth. In this paper we consider a mathematical model for cancer with treatment by using Lotka-Volterra Competition model. In order to minimize the side effects for treatment, we propose a switched system to determine the duration of treatments by using the MDT method and provide an analytical insight into the effectiveness of such method. An illustrative example is presented to show the validity of the results.

Background Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is useful in predicting responses to angiogenic therapy of malignant tumors. Purpose To observe the dynamics of DCE-MRI parameters in evaluating early effects of antiangiogenic therapy in a C6 glioma rat model. Material and Methods The Bevacizumab or vehicle treatment was started from the 14th day after glioma model was established. The treated and control groups (n = 13 per group) underwent DCE-MRI scans on days 0, 1, 3, 5, and 7 after treatment. Tumor volume was calculated according to T2-weighted images. Hematoxylin and eosin, microvessel density (MVD), and proliferating cell nuclear antigen (PCNA) examination were performed on day 7. The MRI parameters between the two groups were compared and correlations with immunohistochemical scores were analyzed. Results The average tumor volume of treated group was significantly lower than that of control group on day 7 (81.764 ± 1.043 vs. 103.634 ± 3.868 mm3, P = 0.002). Ktrans and Kep decreased in the treated group while they increased in the control group. The differences were observed on day 5 (Ktrans: 0.045 ± 0.018 vs. 0.093 ± 0.014 min−1, P < 0.001; Kep: 0.062 ± 0.018 vs. 0.134 ± 0.047 min−1, P = 0.005) and day 7 (Ktrans: 0.032 ± 0.010 vs. 0.115 ± 0.025 min−1, P < 0.001; Kep: 0.045 ± 0.016 vs. 0.144 ± 0.042 min−1, P < 0.001). The difference of Ve was observed on day 5 (0.847 ± 0.248 vs. 0.397 ± 0.151, P = 0.009) and 7 (0.920 ± 0.154 vs. 0.364 ± 0.105, P = 0.006). Ktrans and Kep showed positive correlations with MVD and Ve showed negative correlation with PCNA. Conclusion DCE-MRI can assess the changes of early effects of anti-angiogenic therapy in preclinical practice.

Many research projects are underway to improve the diagnosis and therapy in ophthalmology. Indeed, visual acuity deficits affect 285 million people worldwide and different strategies are being developed to strengthen patient care. One of these strategies is the use of gold nanoparticles (GNP) for their multiple properties and their ability to be used as both diagnosis and therapy tools. This review exhaustively details research developing GNPs for use in ophthalmology. The toxicity of GNPs and their distribution in the eye are described through in vitro and in vivo studies. All publications addressing the pharmacokinetics of GNPs administered in the eye are extensively reviewed. In addition, their use as biosensors or for imaging with optical coherence tomography is illustrated. The future of GNPs for ophthalmic therapy is also discussed. GNPs can be used to deliver genes or drugs through different administration routes. Their antiangiogenic and anti-inflammatory properties are of great interest for different ocular pathologies. Finally, GNPs can be used to improve stereotactic radiosurgery, brachytherapy, and photothermal therapy because of their many properties.

Since the establishment of tumor angiogenesis as a therapeutic target, new, effective antiangiogenic agents have been developed. Despite their demonstrable clinical benefits, these therapies often have only a short-term effect, with limited impact on the overall survival of cancer patients. A question in the development of these drugs concerns their optimal use in combination regimens with newer therapeutic strategies. Here we review the current therapeutic settings combining anti-angiogenesis inhibitors with chemotherapy, PARP inhibitors or immune checkpoint blockers, focusing on ovarian cancer as tumor model.

Introduction: Angiogenesis is a complex process. In fact, it is one of the most important biological events that can be observed with the production of new vessels in many stages of embryonic development and pathological conditions. In pathological conditions such as tumor growth, the progression of the disease is associated with angiogenesis. Therefore, in the present study, the effects of various doses of zinc oxide nanoparticles on chick chorioallantoic membrane (CAM) were assessed. Materials & Methods: In this experimental study, 40 ROSS egg were randomly divided into four groups (controls-group 1-group 2-group 3). After the second day of incubation, a window was opened on the eggs and on the eighth day a gelatin sponge was placed on the chick chorioallantoic membrane. Experimental groups were treated with 500, 1000 and 2000 μg / ml zinc oxide nanoparticles, respectively. On the twelfth day after the incubation, samples were removed from the device and after removing the windows, all of them were viewed using a photo stereomicroscope. Findings: The results showed that zinc oxide nanoparticles significantly reduced the number and length of blood vessels compared to the control sample (P less-than 0.05). The mean length of blood vessels treated with nanoparticles of zinc oxide compared to the control group showed that there was a difference between the treated group with concentration of 500 μg / ml zinc oxide nanoparticle (3.16 ± 0.4 cm) with control group (4.13 ± 0.44 cm) at the level of P less-than 0.05 is significant. Discussion & Conclusion: The results of this study showed that zinc oxide nanoparticles have anti- angiogenesis activity in an in vivo environment. In vivo studies showed that treatment with this nanoparticle inhibited angiogenesis would reduce the number and length of chick chorioallantoic membrane vein.

There is a strong need for non-invasive detection of normal tissue from diseased one and a better understanding of the factors involved in the infection’s growth. Continuous monitoring of tissue samples at different time points is highly desirable. We demonstrate using the photoacoustic spectral response technique (PASR) for in situ analysis in a developing chicken embryo as a model (CAM) for anti-angiogenesis and vascular development. The photoacoustic technique is an emerging modality that is based on the acoustic detection of optical absorption of biological samples. The detected PA signals and their spectral response were used as a signature to determine the vasculature development pathology. Continuous monitoring of vascular growth and an anti-drug (Cisplatin) effect on vasculature has been done. PASR was investigated for the 10th day, 11th day, and 12th day control and inoculated egg samples. It shows that the dominant frequency of the PA spectral response for 10th day control and inoculated eggs lies between 0.45–0.52 MHz, whereas for 11th day and 12th day control eggs lie at 0.61 ± 0.152 MHz and 0.67 ± 0.001 MHz, respectively. The inoculated 11th and 12th day eggs lie at 0.35 ± 0.156 MHz and 0.16 ± 0.004 MHz, respectively. PASR could monitor the change in growth within a span of one day, which was not possible through the conventional imaging approach. This would open up a potential diagnostic technique for continuous monitoring of CAM assays.