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Clinical Efficacy of a Novel Therapeutic Principle, Anakoinosis.

Classic tumor therapy, consisting of cytotoxic agents and/or targeted therapy, has not overcome therapeutic limitations like poor risk genetic parameters, genetic heterogeneity at different metastatic sites or the problem of undruggable targets. Here we summarize data and trials principally following a completely different treatment concept tackling systems biologic processes: the principle of communicative reprogramming of tumor tissues, i.e., anakoinosis (ancient greek for communication), aims at establishing novel communicative behavior of tumor tissue, the hosting organ and organism via re

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… | Metronomic chemotherapy (selected randomized trials) Neoplasia | No pts | Metronomic* chemotherapy | Transcriptional modulators | Small molecule | Best response | Publication Glioblastoma (RANDOMIZED) Glioblastoma (randomized) | 85 | Temozolomide * vs . … Randomized phase II trial of chemoradiotherapy followed by either dose-dense or metronomic temozolomide for newly diagnosed glioblastoma. J. Clin. Oncol. 27, 3861–3867. 10.1200/JCO.2008.20.7944 Coras B., Hafner C., Reichle A., Hohenleutner U., Szeimies R.-M., Landthaler M., et al. (2004). …

[Retracted] miR‑23a suppresses pancreatic cancer cell progression by inhibiting PLK‑1 expression.

BACKGROUND: One presentation of Avoidant/Restrictive Food Intake Disorder (ARFID) is characterized by picky eating, i.e., selective eating based on the sensory properties of food. The present study has two aims. The first is to describe distress and impairment in individuals with ARFID secondary to picky eating. The second is to determine whether eating behaviors hypothesized to be specific to picky eating can differentiate picky eaters with and without ARFID from typical eaters (e.g., individuals not reporting picky or disordered eating) and individuals who strongly endorse attitudes associat

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… Combination of biochanin A and temozolomide impairs tumor growth by modulating cell metabolism in glioblastoma multiforme. Anticancer Res. 2019;39:57–66. doi: 10.21873/anticanres.13079. 57. Robins HI, et al. … Molecular evolution of a glioblastoma controlled with tumor treating fields and concomitant temozolomide. Front. Oncol. 2018;8:451. doi: 10.3389/fonc.2018.00451. 58. Brennan CW, et al. The somatic genomic landscape of glioblastoma. Cell. 2013;155:462–477. doi: 10.1016/j.cell.2013.09.034. 59. …

Cancer treatment using peptides: current therapies and future prospects.

This paper discusses the role of peptides in cancer therapy with special emphasis on peptide drugs which are already approved and those in clinical trials. The potential of peptides in cancer treatment is evident from a variety of different strategies that are available to address the progression of tumor growth and propagation of the disease. Use of peptides that can directly target cancer cells without affecting normal cells (targeted therapy) is evolving as an alternate strategy to conventional chemotherapy. Peptide can be utilized directly as a cytotoxic agent through various mechanisms or

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… For example, cilengitide was used in a phase I/IIa combination trial, which combined cilengitide with radiotherapy and temozolomide for newly diagnosed Glioblastoma patients resulting in better overall survival (OS) rates [ 152 ]. … with concomitant radiotherapy followed by cilengitide and temozolomide maintenance therapy in patients with newly diagnosed glioblastoma Journal of Clinical Oncology 2010 28 16 2712 2718 2-s2.0-77954924659 20439646 10.1200/JCO.2009.26.6650 153 Retter AS Figg WD Dahut WL The combination of antiangiogenic …

Application of dendritic cell extracellular vesicles as a valid nanoparticle platform for cancer therapies: a narrative review.

The prevalence of cancers has actually increased during the last few decades, affecting almost all human societies. Despite progress in therapeutic protocols, cancer is still the main cause of global human mortality. Although the advancement of modern immunotherapeutic approaches can increase the survival rate of cancer patients, new modalities are essential for improved therapeutic outcomes. Extracellular vesicles (EVs) are nanosized particles and are used for cell-free approaches instead of direct whole cell-based administration. It has been thought that EVs can reduce the risks and side eff

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… dendritic cell NCT00125749 Vaccination of Patients with Stage IV Melanoma with Dendritic Cells COMPLETED Melanoma, Neoplasm Metastasis BIOLOGICAL: Dendritic cell vaccination NCT00626483 Basiliximab in Treating Patients with Newly Diagnosed Glioblastoma Multiforme Undergoing Targeted Immunotherapy and Temozolomide-Caused … UNKNOWN Glioblastoma Glioma Neoplasms, Neuroepithelia, Neuroectodermal Tumors Neoplasms, Neoplasms, Nerve Tissue Vaccines Immunologic Factors BIOLOGICAL: Dendritic Cell/Tumor Fusion Vaccine, DRUG: Interleukin-12, DRUG: Temozolomide NCT00937183 Dendritic Cell Vaccine in Treating Patients with Indolent …

Oxidative Stress and Cancer: Harnessing the Therapeutic Potential of Curcumin and Analogues Against Cancer.

Reactive oxygen species (ROS) are a class of bioactive molecules that are the by-products of many cellular functions. These molecules are present in normal cells at homeostatic levels but have been studied extensively in cancer due to their dysregulation resulting in pro- and anti-tumorigenic environments. Completely understanding the paradoxical nature of ROS in cancer is imperative to fully realize its modulation as cancer therapy. Studies into ROS have shown far-reaching effects in cancer, including how ROS levels regulate signaling, response to treatment, drug resistance, etc. Many drugs w

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… Dimethyl Fumarate was studied in concert with Temozolomide and radiation therapy for patients with glioblastoma multiforme in clinical trial NCT02337426 . … Shafer D , Tombes MB , Shrader E , Phase I trial of dimethyl fumarate, temozolomide, and radiation therapy in glioblastoma . Neurooncol Adv . 2020 ; 2 ( 1 ): vdz052 . doi: 10.1093/noajnl/vdz052 32642720 PMC7212848 41. …

Phase 2 Study of Pomalidomide (CC-4047) Monotherapy for Children and Young Adults With Recurrent or Progressive Primary Brain Tumors.

IntroductionTreatment of recurrent primary pediatric brain tumors remains a major challenge, with most children succumbing to their disease. We conducted a prospective phase 2 study investigating the safety and efficacy of pomalidomide (POM) in children and young adults with recurrent and progressive primary brain tumors.MethodsPatients with recurrent and progressive high-grade glioma (HGG), diffuse intrinsic pontine glioma (DIPG), ependymoma, or medulloblastoma received POM 2.6 mg/m2/day (the recommended phase 2 dose [RP2D]) on days 1-21 of a 28-day cycle. A Simon's Optimal 2-stage design was

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… A phase 1 trial examined the combination of dasatinib, lenalidomide, and temozolomide in pediatric patients with either relapsed or refractory CNS tumors ( 27 ). … Phase I trial of dasatinib, lenalidomide, and temozolomide in children with relapsed or refractory central nervous system tumors. J Neurooncol (2018) 138(1):199–207. 10.1007/s11060-018-2791-y 28. Terry RL, Meyran D, Ziegler DS, Haber M, Ekert PG, Trapani JA, et al. …

Breaking Therapy Resistance: An Update on Oncolytic Newcastle Disease Virus for Improvements of Cancer Therapy.

Resistance to therapy is a major obstacle to cancer treatment. It may exist from the beginning, or it may develop during therapy. The review focusses on oncolytic Newcastle disease virus (NDV) as a biological agent with potential to break therapy resistance. This avian virus combines, upon inoculation into non-permissive hosts such as human, 12 described anti-neoplastic effects with 11 described immune stimulatory properties. Fifty years of clinical application of NDV give witness to the high safety profile of this biological agent. In 2015, an important milestone was achieved, namely the succ

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… (iii) Multidrug resistance, particularly resistance to temozolomide (TMZ), is a challenge in the treatment of GBM. NDV was found to enhance the growth-inhibiting and proapoptotic effects of TMZ on GBM cells in vitro and in vivo [ 106 ]. … Two examples are cyclophosphamide (CPA) and Temozolomide (TMZ). CPA has been used successfully in combination with OVs including HSV-1, adenovirus, vaccinia virus, reovirus, measles, and vesicular stomatitis virus. …

Management of belantamab mafodotin-associated corneal events in patients with relapsed or refractory multiple myeloma (RRMM).

Belantamab mafodotin (belamaf) demonstrated deep and durable responses in patients with heavily pretreated relapsed or refractory multiple myeloma (RRMM) in DREAMM-2 (NCT03525678). Corneal events, specifically keratopathy (including superficial punctate keratopathy and/or microcyst-like epithelial changes (MECs), eye examination findings with/without symptoms), were common, consistent with reports from other antibody-drug conjugates. Given the novel nature of corneal events in RRMM management, guidelines are required for their prompt identification and appropriate management. Eye examination f

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… Safety, pharmacokinetics, and antitumor response of depatuxizumab mafodotin as monotherapy or in combination with temozolomide in patients with glioblastoma. Neuro. Oncol. 2018;20:838–847. doi: 10.1093/neuonc/nox202. 39. Lassman AB, et al. … Safety and efficacy of depatuxizumab mafodotin + temozolomide in patients with EGFR-amplified, recurrent glioblastoma: results from an international phase I multicenter trial. Neuro. Oncol. 2019;21:106–114. doi: 10.1093/neuonc/noy091. 40. van den Bent M, et al. …

Cannabidiol (CBD) in Cancer Management.

The plant Cannabis sativa has been in use medicinally for several thousand years. It has over 540 metabolites thought to be responsible for its therapeutic effects. Two of the key phytocannabinoids are cannabidiol (CBD) and tetrahydrocannabinol (THC). Unlike THC, CBD does not have potentially intoxicating effects. Preclinical and clinical research indicates that CBD has a wide range of therapeutic effects, and many of them are relevant to the management of cancer. In this article, we explore some of the potential mechanisms of action of CBD in cancer, and evidence of its efficacy in the integr

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… THC has been found to enhance the effects of temozolomide in mice glioma xenografts, including in temozolomide-resistant tumours (the combination enhanced autophagy), and without toxic side effects [ 198 ]. … Brain tumour treatment, including glioblastoma, utilises external beam radiation therapy alone or in combination with chemotherapy (e.g., temozolomide), however this treatment can cause severe damage to normal brain tissues (especially adult neurons and endothelial cells). …

Intravenous Vitamin C for Cancer Therapy - Identifying the Current Gaps in Our Knowledge.

The use of intravenous vitamin C (IVC) for cancer therapy has long been an area of intense controversy. Despite this, high dose IVC has been administered for decades by complementary health care practitioners and physicians, with little evidence base resulting in inconsistent clinical practice. In this review we pose a series of questions of relevance to both researchers and clinicians, and also patients themselves, in order to identify current gaps in our knowledge. These questions include: Do oncology patients have compromised vitamin C status? Is intravenous the optimal route of vitamin C a

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… Animal studies have indicated that concurrent administration of vitamin C to numerous different chemotherapeutic agents (e.g., gemcitabine, paclitaxel, carboplatin, melphalan, carfilzomib, bortezomib, cisplatin, and temozolomide) synergistically decreased xenograft tumor growth, including in a chemotherapy … 7.5 g/d once per week for at least 4 weeks | Case control | Breast cancer with radiotherapy and/or chemotherapy | Decreased complaints No adverse side effects | Vollbracht et al., 2011 IVC 75–87.5 g/d two to three times per week for up to 35 weeks | Single arms | Glioblastoma with radiotherapy and temozolomide …

Synthetic lethality and DNA damage response targeting in cancer stem cells: a comprehensive review.

This comprehensive review explores the critical intersection of Synthetic Lethality (SL) and DNA Damage Response (DDR) targeting within Cancer Stem Cells (CSCs), a subpopulation central to tumor initiation, metastasis, and therapeutic resistance. CSCs exhibit unique biological properties, including enhanced DNA repair mechanisms and metabolic plasticity, rendering them intrinsically resistant to conventional therapies. The fundamental mechanisms of DDR pathways and their dysregulation in cancer are delineated, highlighting how these vulnerabilities can be exploited through SL. The review synth

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… Clinical trials ongoing [ 37 ] GD3 Glioblastoma, Breast Cancer Promotes cell growth, plasticity, clonogenicity, tumorigenicity, migration Chemotherapy resistance (Temozolomide) Potential therapeutic target, especially via ST8SIA1 inhibition [ 38 ] Lewis Y Small Cell Lung Cancer Blood group antigen, potential … Clinical trials ongoing | [ 37 ] GD3 | Glioblastoma, Breast Cancer | Promotes cell growth, plasticity, clonogenicity, tumorigenicity, migration | Chemotherapy resistance (Temozolomide) | Potential therapeutic target, especially via ST8SIA1 inhibition | [ 38 ] Lewis Y | Small Cell Lung Cancer | Blood …

The investigation of oncolytic viruses in the field of cancer therapy.

Oncolytic viruses (OVs) have emerged as a potential strategy for tumor treatment due to their ability to selectively replicate in tumor cells, induce apoptosis, and stimulate immune responses. However, the therapeutic efficacy of single OVs is limited by the complexity and immunosuppressive nature of the tumor microenvironment (TME). To overcome these challenges, engineering OVs has become an important research direction. This review focuses on engineering methods and multi-modal combination therapies for OVs aimed at addressing delivery barriers, viral phagocytosis, and antiviral immunity in

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… Temozolomide (TMZ), another alkylating agent and immunomodulator, is extensively employed in treating various solid tumors such as glioma and melanoma. … MV-NIS, oncolytic measles virus encoding thyroidal sodium iodide symporter; NIS, VSV-hIFNbeta-sodium iodide symporter; Pexa-Vec, pexastimogene devacirepvec; TMZ, Temozolomide; HER2, human epidermal growth factor receptor. …

Tumor microenvironment and exosomes in brain metastasis: Molecular mechanisms and clinical application.

Metastasis is one of the important biological features of malignant tumors and one of the main factors responsible for poor prognosis. Although the widespread application of newer clinical technologies and their continuous development have significantly improved survival in patients with brain metastases, there is no uniform standard of care. More effective therapeutic measures are therefore needed to improve prognosis. Understanding the mechanisms of tumor cell colonization, growth, and invasion in the central nervous system is of particular importance for the prevention and treatment of brai

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… Murphy et al. ( 42 ) found that connexin 43 can induce resistance to temozolomide by activating the AKT/AMP-activated protein kinase/mammalian target of rapamycin signaling pathway in malignant gliomas. … Macitentan, a dual endothelin receptor antagonist, in combination with temozolomide leads to glioblastoma regression and long-term survival in mice . …

Targeting Histone Epigenetic Modifications and DNA Damage Responses in Synthetic Lethality Strategies in Cancer?

Synthetic lethality strategies are likely to be integrated in effective and specific cancer treatments. These strategies combine different specific targets, either in similar or cooperating pathways. Chromatin remodeling underlies, directly or indirectly, all processes of tumor biology. In this context, the combined targeting of proteins associated with different aspects of chromatin remodeling can be exploited to find new alternative targets or to improve treatment for specific individual tumors or patients. There are two major types of proteins, epigenetic modifiers of histones and nuclear o

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… In some particular contexts, such as those associated with DNA damage targeting strategies, the inhibition of HDAC sensitizes neuroblastoma cells to etoposide, melphalan or carboplatin [ 95 ] and melanoma cells to temozolomide [ 96 ]. … VRK1 Depletion Facilitates the Synthetic Lethality of Temozolomide and Olaparib in Glioblastoma Cells. Front. Cell Dev. Biol. 2021;9:683038. doi: 10.3389/fcell.2021.683038. 124. Campillo-Marcos I., Lazo P.A. …

Chimeric antigen receptor (CAR) immunotherapy: basic principles, current advances, and future prospects in neuro-oncology.

With recent advances, chimeric antigen receptor (CAR) immunotherapy has become a promising modality for patients with refractory cancer diseases. The successful results of CAR T cell therapy in relapsed and refractory B-cell malignancies shifted the paradigm of cancer immunotherapy by awakening the scientific, clinical, and commercial interest in translating this technology for the treatment of solid cancers. This review elaborates on fundamental principles of CAR T cell therapy (development of CAR construct, challenges of CAR T cell therapy) and its application on solid tumors as well as CAR

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… The current standard therapy for GBM includes maximal surgical resection with consecutive radiotherapy and adjuvant chemotherapy with temozolomide (TMZ). … cycles | 12/May 2022 | Second Affiliated Hospital, School of Medicine, Zhejiang University | NCT04385173 I/II | Three locoregional or intracerebroventricular injections of CAR T cells at two doses between temozolomide cycles | 40/June 2024 | Second Affiliated Hospital of Zhejiang | NCT04077866 GD2 | …

Corneal Epithelial Findings in Patients with Multiple Myeloma Treated with Antibody-Drug Conjugate Belantamab Mafodotin in the Pivotal, Randomized, DREAMM-2 Study.

IntroductionPatients with relapsed or refractory multiple myeloma (RRMM) represent an unmet clinical need. Belantamab mafodotin (belamaf; GSK2857916) is a first-in-class antibody-drug conjugate (ADC; or immunoconjugate) that delivers a cytotoxic payload, monomethyl auristatin F (MMAF), to myeloma cells. In the phase II DREAMM-2 study (NCT03525678), single-agent belamaf (2.5 mg/kg) demonstrated clinically meaningful anti-myeloma activity (overall response rate 32%) in patients with heavily pretreated disease. Microcyst-like epithelial changes (MECs) were common, consistent with reports from oth

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… Gan HK Reardon DA Lassman AB Safety, pharmacokinetics, and antitumor response of depatuxizumab mafodotin as monotherapy or in combination with temozolomide in patients with glioblastoma Neuro Oncol 2018 20 838 847 29077941 10.1093/neuonc/nox202 PMC5961429 23. … Reardon DA Lassman AB van den Bent M Efficacy and safety results of ABT-414 in combination with radiation and temozolomide in newly diagnosed glioblastoma Neuro Oncol 2017 19 965 975 28039367 10.1093/neuonc/now257 PMC5570193 30. …

The proteasome as a druggable target with multiple therapeutic potentialities: Cutting and non-cutting edges.

Ubiquitin Proteasome System (UPS) is an adaptable and finely tuned system that sustains proteostasis network under a large variety of physiopathological conditions. Its dysregulation is often associated with the onset and progression of human diseases; hence, UPS modulation has emerged as a promising new avenue for the development of treatments of several relevant pathologies, such as cancer and neurodegeneration. The clinical interest in proteasome inhibition has considerably increased after the FDA approval in 2003 of bortezomib for relapsed/refractory multiple myeloma, which is now used in

Whole brain radiotherapy combined with intrathecal liposomal cytarabine for leptomeningeal metastasis-a safety analysis and validation of the EANO-ESMO classification.

BackgroundAlthough there is no proven standard therapy for leptomeningeal metastases (LM), treatment often includes intrathecal chemotherapy combined with whole brain radiation therapy (WBRT). Little is known about the toxicity of such combination therapies. We performed a retrospective safety analysis for the combination of intrathecal liposomal cytarabine with WBRT in patients with LM and validated the EANO-ESMO (European Association of Neuro-oncology-European Society for Medical Oncology) classification in this unique cohort.MethodsTreatment toxicities in patients diagnosed with LM between

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… a Median (range) b Absolute number (percentage) c Non-solid: non-Hodgkin lymphoma, multiple myeloma d Others: colorectal cancer, gastric cancer, esophageal cancer, uterine cancer, ovarian cancer, rhabdomyosarcoma, glioblastoma, malignant melanoma e Concomitant systemic pharmacotherapy: Vemurafenib, Temozolomide … a Median (range) b Absolute number (percentage) c Non-solid: non-Hodgkin lymphoma, multiple myeloma d Others: colorectal cancer, gastric cancer, esophageal cancer, uterine cancer, ovarian cancer, rhabdomyosarcoma, glioblastoma, malignant melanoma e Concomitant systemic pharmacotherapy: Vemurafenib, Temozolomide …

A Phase II Study of the Efficacy and Safety of Oral Selinexor in Recurrent Glioblastoma.

PURPOSE: Selinexor is an oral selective inhibitor of exportin-1 (XPO1) with efficacy in various solid and hematologic tumors. We assessed intratumoral penetration, safety, and efficacy of selinexor monotherapy for recurrent glioblastoma. PATIENTS AND METHODS: Seventy-six adults with Karnofsky Performance Status ≥ 60 were enrolled. Patients undergoing cytoreductive surgery received up to three selinexor doses (twice weekly) preoperatively (Arm A; n = 8 patients). Patients not undergoing surgery received 50 mg/m2 (Arm B, n = 24), or 60 mg (Arm C, n = 14) twice weekly, or 80 mg once weekly (Arm

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… Study participants Male or female patients aged at least 18 years with a locally determined diagnosis of GBM ( 11 ) and recurrence/progression after at least radiotherapy and temozolomide were eligible. … Patients had received a median of one prior therapy in addition to radiotherapy and temozolomide (range 1–8), and the median KPS was 90 (range 60–100). The median age at the time of enrollment was 56 years, and 71% of patients were men ( Table 1 ). Table 1. Patient characteristics. …

LncRNA RHPN1-AS1 Targeting miR-625/REG3A Promotes Cell Proliferation And Invasion Of Glioma Cells.

IntroductionGlioma arises from the proliferation of neuroglial cells differentiated from the ectoderm. Evidence has confirmed that differentially expressed long non-coding RNAs (lncRNAs) may be involved in the development and progression of various tumors. The present study aimed to explore the biological function of lncRNA RHPN1-AS1 in glioma.Materials and methodsThe expressions of RHPN1-AS1 in glioma tissues and cells were examined using RT-PCR. Colony formation assay, MTT assay, wound healing assay and transwell assay were performed to detect cell cloning efficiency, proliferation, migratio

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… a variety of complex tumors is generally referred to as “glioma”. 3 , 4 The incidence of gliomas ranges from 3 to 8 per 100,000 people in China while the global morbidity ranges from 4.67 to 5.73 per 100,000 people. 5 , 6 At present, the standard treatment of glioma is concurrent chemotherapy with temozolomide … XRCC3 contributes to temozolomide resistance of glioblastoma cells by promoting DNA double-strand break repair . Cancer Lett . 2018 ; 424 : 119 – 126 . doi: 10.1016/j.canlet.2018.03.025 29574277 14. Ransohoff JD , Wei Y , Khavari PA . …