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1. The application of electrosprayed minocycline‐loaded PLGA microparticles for the treatment of glioblastoma

   https://doi.org/10.1002/bit.28527  

   Arriaga, Marco A; Amieva, Juan A; Quintanilla, Jaqueline; Jimenez, Angela; Ledezma, Julio; Lopez, Silverio; Martirosyan, Karen S; Chew, Sue Anne (November 2023, Biotechnology and Bioengineering)

   Abstract The survival of patients with glioblastoma multiforme (GBM), the most common and invasive form of malignant brain tumors, remains poor despite advances in current treatment methods including surgery, radiotherapy, and chemotherapy. Minocycline is a semi‐synthetic tetracycline derivative that has been widely used as an antibiotic and more recently, it has been utilized as an antiangiogenic factor to inhibit tumorigenesis. The objective of this study was to investigate the utilization of electrospraying process to fabricate minocycline‐loaded poly(lactic‐co‐glycolic acid) (PLGA) microparticles with high drug loading and loading efficiency and to evaluate their ability to induce cell toxicity in human glioblastoma (i.e., U87‐MG) cells. The results from this study demonstrated that solvent mixture of dicholoromethane (DCM) and methanol is the optimal solvent combination for minocycline and larger amount of methanol (i.e., 70:30) resulted in a higher drug loading. All three solvent ratios of DCM:methanol tested produced microparticles that were both spherical and smooth, all in the micron size range. The electrosprayed microparticles were able to elicit a cytotoxic response in U87‐MG glioblastoma cells at a lower concentration of drug compared to the free drug. This work provides proof of concept to the hypothesis that electrosprayed minocycline‐loaded PLGA microparticles can be a promising agent for the treatment of GBM and could have potential application for cancer therapies. 

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2. In Vitro and In Vivo Enhancement of Temozolomide Effect in Human Glioblastoma by Non-Invasive Application of Cold Atmospheric Plasma

   https://doi.org/10.3390/cancers13174485  

   Soni, Vikas; Adhikari, Manish; Simonyan, Hayk; Lin, Li; Sherman, Jonathan H.; Young, Colin N.; Keidar, Michael (September 2021, Cancers)

   null (Ed.)

   Glioblastoma (GBM) is one of the most aggressive forms of adult brain cancers and is highly resistant to treatment, with a median survival of 12–18 months after diagnosis. The poor survival is due to its infiltrative pattern of invasion into the normal brain parenchyma, the diffuse nature of its growth, and its ability to quickly grow, spread, and relapse. Temozolomide is a well-known FDA-approved alkylating chemotherapy agent used for the treatment of high-grade malignant gliomas, and it has been shown to improve overall survival. However, in most cases, the tumor relapses. In recent years, CAP has been used as an emerging technology for cancer therapy. The purpose of this study was to implement a combination therapy of CAP and TMZ to enhance the effect of TMZ and apparently sensitize GBMs. In vitro evaluations in TMZ-sensitive and resistant GBM cell lines established a CAP chemotherapy enhancement and potential sensitization effect across various ranges of CAP jet application. This was further supported with in vivo findings demonstrating that a single CAP jet applied non-invasively through the skull potentially sensitizes GBM to subsequent treatment with TMZ. Gene functional enrichment analysis further demonstrated that co-treatment with CAP and TMZ resulted in a downregulation of cell cycle pathway genes. These observations indicate that CAP can be potentially useful in sensitizing GBM to chemotherapy and for the treatment of glioblastoma as a non-invasive translational therapy. 

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3. Glioblastoma and Methionine Addiction

   https://doi.org/10.3390/ijms23137156  

   Sowers, Mark L.; Sowers, Lawrence C. (July 2022, International Journal of Molecular Sciences)

   Glioblastoma is a fatal brain tumor with a bleak prognosis. The use of chemotherapy, primarily the alkylating agent temozolomide, coupled with radiation and surgical resection, has provided some benefit. Despite this multipronged approach, average patient survival rarely extends beyond 18 months. Challenges to glioblastoma treatment include the identification of functional pharmacologic targets as well as identifying drugs that can cross the blood-brain barrier. To address these challenges, current research efforts are examining metabolic differences between normal and tumor cells that could be targeted. Among the metabolic differences examined to date, the apparent addiction to exogenous methionine by glioblastoma tumors is a critical factor that is not well understood and may serve as an effective therapeutic target. Others have proposed this property could be exploited by methionine dietary restriction or other approaches to reduce methionine availability. However, methionine links the tumor microenvironment with cell metabolism, epigenetic regulation, and even mitosis. Therefore methionine depletion could result in complex and potentially undesirable responses, such as aneuploidy and the aberrant expression of genes that drive tumor progression. If methionine manipulation is to be a therapeutic strategy for glioblastoma patients, it is essential that we enhance our understanding of the role of methionine in the tumor microenvironment. 

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4. Assessment of brain cancer atlas maps with multimodal imaging features

   https://doi.org/10.1186/s12967-023-04222-3  

   Capobianco, Enrico; Dominietto, Marco (December 2023, Journal of Translational Medicine)

   Abstract Background Glioblastoma Multiforme (GBM) is a fast-growing and highly aggressive brain tumor that invades the nearby brain tissue and presents secondary nodular lesions across the whole brain but generally does not spread to distant organs. Without treatment, GBM can result in death in about 6 months. The challenges are known to depend on multiple factors: brain localization, resistance to conventional therapy, disrupted tumor blood supply inhibiting effective drug delivery, complications from peritumoral edema, intracranial hypertension, seizures, and neurotoxicity. Main text Imaging techniques are routinely used to obtain accurate detections of lesions that localize brain tumors. Especially magnetic resonance imaging (MRI) delivers multimodal images both before and after the administration of contrast, which results in displaying enhancement and describing physiological features as hemodynamic processes. This review considers one possible extension of the use of radiomics in GBM studies, one that recalibrates the analysis of targeted segmentations to the whole organ scale. After identifying critical areas of research, the focus is on illustrating the potential utility of an integrated approach with multimodal imaging, radiomic data processing and brain atlases as the main components. The templates associated with the outcome of straightforward analyses represent promising inference tools able to spatio-temporally inform on the GBM evolution while being generalizable also to other cancers. Conclusions The focus on novel inference strategies applicable to complex cancer systems and based on building radiomic models from multimodal imaging data can be well supported by machine learning and other computational tools potentially able to translate suitably processed information into more accurate patient stratifications and evaluations of treatment efficacy. Graphical Abstract 

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5. Microengineered 3D Tumor Models for Anti-Cancer Drug Discovery in Female-Related Cancers

   https://doi.org/10.1007/s10439-020-02704-9  

   Amirghasemi, Farbod; Adjei-Sowah, Emmanuela; Pockaj, Barbara A.; Nikkhah, Mehdi (January 2021, Annals of Biomedical Engineering)

   null (Ed.)

   The burden of cancer continues to increase in society and negatively impacts the lives of numerous patients. Due to the high cost of current treatment strategies, there is a crucial unmet need to develop inexpensive preclinical platforms to accelerate the process of anti-cancer drug discovery to improve outcomes in cancer patients, most especially in female patients. Many current methods employ expensive animal models which not only present ethical concerns but also do not often accurately predict human physiology and the outcomes of anti-cancer drug responsiveness. Conventional treatment approaches for cancer generally include systemic therapy after a surgical procedure. Although this treatment technique is effective, the outcome is not always positive due to various complex factors such as intratumor heterogeneity and confounding factors within the tumor microenvironment (TME). Patients who develop metastatic disease still have poor prognosis. To that end, recent efforts have attempted to use 3D microengineered platforms to enhance the predictive power and efficacy of anti-cancer drug screening, ultimately to develop personalized therapies. Fascinating features of microengineered assays, such as microfluidics, have led to the advancement in the development of the tumor-on-chip technology platforms, which have shown tremendous potential for meaningful and physiologically relevant anti-cancer drug discovery and screening. Three dimensional microscale models provide unprecedented ability to unveil the biological complexities of cancer and shed light into the mechanism of anti-cancer drug resistance in a timely and resource efficient manner. In this review, we discuss recent advances in the development of microengineered tumor models for anti-cancer drug discovery and screening in female-related cancers. We specifically focus on female-related cancers to draw attention to the various approaches being taken to improve the survival rate of women diagnosed with cancers caused by sex disparities. We also briefly discuss other cancer types like colon adenocarcinomas and glioblastoma due to their high rate of occurrence in females, as well as the high likelihood of sex-biased mutations which complicate current treatment strategies for women. We highlight recent advances in the development of 3D microscale platforms including 3D tumor spheroids, microfluidic platforms as well as bioprinted models, and discuss how they have been utilized to address major challenges in the process of drug discovery, such as chemoresistance, intratumor heterogeneity, drug toxicity, etc. We also present the potential of these platform technologies for use in high-throughput drug screening approaches as a replacements of conventional assays. Within each section, we will provide our perspectives on advantages of the discussed platform technologies. 

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