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Topic Review
Fundamental Principles in Electromotive Enhanced Drug Administration
Local-regional administration of cytotoxic drugs is an important adjunct to systemic chemotherapy amongst cancer patients. It allows for targeted delivery of agents at high concentration to target sites while minimizing systemic side effects. Despite the pharmacokinetic advantages of the local–regional approach, drug transport into tumor nodules remains limited due to the biophysical properties of these tissues. Electromotive enhanced drug administration (EMDA) represents a potential solution to overcome challenges in local drug transport by applying electric currents. Through electrokinetic phenomena of electromigration, electroosmosis and electroporation, electric currents have been shown to improve drug penetration and distribution in a wide variety of clinical applications.
  • 1.7K
  • 26 Oct 2022
Topic Review
Lynch Syndrome (LS)
Lynch syndrome (LS), also known as Hereditary Non-Polyposis Colorectal Cancer (HNPCC), is an autosomal dominant cancer syndrome which causes about 2–3% of cases of colorectal carcinoma. The development of LS is due to the genetic and epigenetic inactivation of genes involved in the DNA mismatch repair (MMR) system, causing an epiphenomenon known as microsatellite instability (MSI). 
  • 1.7K
  • 22 Aug 2023
Topic Review
Glioblastoma Organoids
Glioblastoma (GB) is the most lethal primary adult brain tumor. The great number of mutations involved and the aggressiveness of glioblastoma render this type of cancer especially difficult to investigate. Moreover, the lack of reliable GB models, together with its considerable clinical heterogeneity, has impaired a comprehensive investigation of the mechanisms that lead to tumorigenesis, cancer progression, and response to treatments. To address this problem, cerebral organoids have emerged as promising tools to investigate brain biology and to recapitulates the major steps involved in glioblastoma tumorigenesis. Here we exemplify relevant aspects of 3D models of glioblastoma, with a specific focus on organoids and their involvement in basic and translational research.
  • 1.7K
  • 25 Nov 2020
Topic Review
Medicinal Plants with Anti-Leukemic Effects
Leukemia is a leukocyte cancer that is characterized by anarchic growth of immature immune cells in the bone marrow, blood and spleen. There are many forms of leukemia, and the best course of therapy and the chance of a patient’s survival depend on the type of leukemic disease. Different forms of drugs have been used to treat leukemia. Due to the adverse effects associated with such therapies and drug resistance, the search for safer and more effective drugs remains one of the most challenging areas of research. Thus, new therapeutic approaches are important to improving outcomes. Almost half of the drugs utilized nowadays in treating cancer are from natural products and their derivatives. Medicinal plants have proven to be an effective natural source of anti-leukemic drugs. The cytotoxicity and the mechanisms underlying the toxicity of these plants to leukemic cells and their isolated compounds were investigated.
  • 1.7K
  • 18 May 2021
Topic Review
Superficial Spindle Cell Mesenchymal Tumors
Superficial spindle cell mesenchymal tumors form a diverse group of lesions with benign and malignant entities that are often very similar clinically and/or histologically. In children, the patient’s age; the lesion site; the presentation as a mass, nodule, or plaque; and the location in the dermis or subcutis are important features that will guide the dermatologist and the pathologist.
  • 1.7K
  • 02 Oct 2021
Topic Review
Cutting-Edge: Preclinical and Clinical Development of Opdualag
Immune checkpoint inhibitors (ICIs) have revolutionized medical practice in oncology since the FDA approval of the first ICI 11 years ago. In light of this, Lymphocyte-Activation Gene 3 (LAG-3) is one of the most important next-generation immune checkpoint molecules, playing a similar role as Programmed cell Death protein 1 (PD-1) and Cytotoxic T-Lymphocyte Antigen 4 (CTLA-4). 19 LAG-3 targeting molecules are being evaluated at 108 clinical trials which are demonstrating positive results, including promising bispecific molecules targeting LAG-3 simultaneously with other ICIs. Recently, a new dual anti-PD-1 (Nivolumab) and anti-LAG-3 (Relatimab) treatment developed by Bristol Myers Squibb (Opdualag), was approved by the Food and Drug Administration (FDA) as the first LAG-3 blocking antibody combination for unresectable or metastatic melanoma. This novel immunotherapy combination more than doubled median progression-free survival (PFS) when compared to nivolumab monotherapy (10.1 months versus 4.6 months).
  • 1.7K
  • 10 Aug 2022
Topic Review
PTEN in different TME compartments
Mounting preclinical and clinical evidence indicates that rewiring the host immune system in favor of an antitumor microenvironment achieves remarkable clinical efficacy in the treatment of many hematological and solid cancer patients. Nevertheless, despite the promising development of many new and interesting therapeutic strategies, many of these still fail from a clinical point of view, probably due to the lack of prognostic and predictive biomarkers. In that respect, several data shed new light on the role of the tumor suppressor phosphatase and tensin homolog on chromosome 10 (PTEN) in affecting the composition and function of the tumor microenvironment (TME) as well as resistance/sensitivity to immunotherapy. In this review, we summarize current knowledge on PTEN functions in different TME compartments (immune and stromal cells) and how they can modulate sensitivity/resistance to different immunological manipulations and ultimately influence clinical response to cancer immunotherapy
  • 1.7K
  • 04 Aug 2020
Topic Review
CCL21/CCR7 in Breast Cancer
Breast cancer is a leading cause of cancer-related deaths worldwide, predominantly caused by metastasis. It is generally accepted that the pattern of breast cancer metastasis is largely determined by the interaction between the chemokine receptors on cancer cells and the chemokines expressed at the sites of metastatic disease. Chemokine receptors belong to the G-protein-coupled receptors (GPCRs) family that appear to be implicated in inflammatory diseases, tumor growth and metastasis. One of its members, C-C Chemokine receptor 7 (CCR7), binds chemokines CCL19 and CCL21, which are important for tissue homeostasis, immune surveillance and tumorigenesis. These receptors have been shown to induce the pathobiology of breast cancer due to their ability to induce cellular proliferation and migration upon the binding of the cognate chemokine receptors. The underlying signaling pathways and exact cellular interactions within this biological system are not fully understood and need further insights.
  • 1.7K
  • 25 May 2021
Topic Review
Thrombospondin-1 in the Tumor Microenvironment
The identification of thrombospondin-1 as an angiogenesis inhibitor in 1990 prompted interest in its role in cancer biology and potential as a therapeutic target. Decreased thrombospondin-1 mRNA and protein expression are associated with progression in several cancers, while expression by nonmalignant cells in the tumor microenvironment and circulating levels in cancer patients can be elevated. THBS1 is not a tumor suppressor gene, but the regulation of its expression in malignant cells by oncogenes and tumor suppressor genes mediates some of their effects on carcinogenesis, tumor progression, and metastasis. In addition to regulating angiogenesis and perfusion of the tumor vasculature, thrombospondin-1 limits antitumor immunity by CD47-dependent regulation of innate and adaptive immune cells. Conversely, thrombospondin-1 is a component of particles released by immune cells that mediate tumor cell killing. Thrombospondin-1 differentially regulates the sensitivity of malignant and nonmalignant cells to genotoxic stress caused by radiotherapy and chemotherapy. 
  • 1.7K
  • 23 Jun 2021
Topic Review
P53
While viewed as the “guardian of the genome”, the importance of the tumor suppressor p53 protein has increasingly gained ever more recognition in modulating additional modes of action related to cell death. Slowly but surely, its importance has evolved from a mutated genetic locus heavily implicated in a wide array of cancer types to modulating lysosomal-mediated cell death either directly or indirectly through the transcriptional regulation of the key signal transduction pathway intermediates involved in this. Taken with its ability to directly modulate mitochondrial outer-membrane permeabilization (and cell death) collectively highlights the complex role that this protein undertakes at the molecular level
  • 1.7K
  • 07 Dec 2020
Topic Review
Targeting PI3K/Akt/mTOR in AML
Acute myeloid leukemia (AML) is a highly heterogeneous hematopoietic malignancy, characterized by excessive proliferation and accumulation of immature myeloid blasts in the bone marrow. While reductions of bulk malignant cells can be achieved in the majority of patients by standard chemotherapy consisting of cell cycle active drugs, such as cytarabine and anthracyclines, approximately two-thirds of patients relapse after the induction therapy, highlighting an unmet need for a more targeted therapeutic approach. A rare population of therapy-resistant cells are believed to be the origin of relapse, termed leukemia stem cells (LSCs), also referred to as leukemia-initiating cells (LICs). These cells acquire enhanced self-renewal capacity and exhibit a block in differentiation.
  • 1.7K
  • 23 Sep 2020
Topic Review
Genomics-Driven Precision Medicine in Pediatric Solid Tumors
The detection of genomic aberrations in cancers has yielded a wealth of information to discover oncogenic drivers or pathogenic variants that are relevant for the development of precise treatment strategies. Studies have shown promising outcomes in adult cancer patients with well characterized cancer genetic biomarkers.
  • 1.7K
  • 17 Mar 2023
Topic Review
Colon Fibroblasts and Inflammation
Colorectal cancer (CRC) is the third most common cause of cancer-related death. Patients suffering inflammatory bowel disease have an increased risk of CRC. It is admitted that CRC found its origin within crypts of the colon mucosa, which host the intestinal stem cells (ISCs) responsible of the tissue renewal. ISC behavior is controlled by the fibroblasts that surround the crypt. During inflammation, the signals delivered by fibroblasts are altered, leading to stem cells’ dysregulation, possibly turning them into cancer-initiating cells.
  • 1.7K
  • 23 Jun 2021
Topic Review
ACT Therapy for Solid Tumors
Adoptive cell therapy (ACT) with tumor-infiltrating T cells (TILs) has emerged as a promising therapy for the treatment of unresectable or metastatic solid tumors. One challenge to finding a universal anticancer treatment is the heterogeneity present between different tumors as a result of genetic instability associated with tumorigenesis. As the epitome of personalized medicine, TIL-ACT bypasses the issue of intertumoral heterogeneity by utilizing the patient’s existing antitumor immune response. Despite being one of the few therapies capable of inducing durable, complete tumor regression, many patients fail to respond. Recent research has focused on increasing therapeutic efficacy by refining various aspects of the TIL protocol, which includes the isolation, ex vivo expansion, and subsequent infusion of tumor specific lymphocytes.
  • 1.7K
  • 05 May 2021
Topic Review
Proteasome Inhibitors
Proteasome inhibitors have shown relevant clinical activity in several hematological malignancies, namely in multiple myeloma and mantle cell lymphoma, improving patient outcomes such as survival and quality of life, when compared with other therapies. However, initial response to the therapy is a challenge as most patients show an innate resistance to proteasome inhibitors, and those that respond to the therapy usually develop late relapses suggesting the development of acquired resistance. The mechanisms of resistance to proteasome inhibition are still controversial and scarce in the literature.
  • 1.7K
  • 18 Apr 2022
Topic Review
Esophageal and Gastric Tumors
Gastric and esophageal tumors are diverse neoplasms that involve mucosal and submucosal tissue layers and include squamous cell carcinomas, adenocarcinomas, spindle cell neoplasms, neuroendocrine tumors, marginal B cell lymphomas, along with less common tumors. The worldwide burden of esophageal and gastric malignancies is significant, with esophageal and gastric cancer representing the ninth and fifth most common cancers, respectively. The approach to diagnosis and staging of these lesions is multimodal and includes a combination of gastrointestinal endoscopy, endoscopic ultrasound, and cross-sectional imaging. Likewise, therapy is multidisciplinary and combines therapeutic endoscopy, surgery, radiotherapy, and systemic chemotherapeutic tools. Future directions for diagnosis of esophageal and gastric malignancies are evolving rapidly and will involve advances in endoscopic and endosonographic techniques including tethered capsules, optical coherence tomography, along with targeted cytologic and serological analyses. 
  • 1.7K
  • 23 Feb 2021
Topic Review
STEAP1–4 and Prostate Cancer
Six-Transmembrane Epithelial Antigen of the Prostate 1–4 (STEAP1–4) compose a family of metalloproteinases involved in iron and copper homeostasis and other cellular processes. In prostate cancer, STEAP1, STEAP2, and STEAP4 are overexpressed, while STEAP3 expression is downregulated. STEAP1–4 can be used as a biomarker and therapeutic target for prostate cancer.
  • 1.7K
  • 24 Aug 2022
Topic Review
Anticancer Activity of Berberine
Berberine is a plant metabolite belonging to the group of isoquinoline alkaloids with strong biological and pharmacological activity. Currently, berberine is receiving considerable interest due to its anticancer activity based on many biochemical pathways, especially its proapoptotic and anti-inflammatory activity. Therefore, the growing number of papers on berberine demands summarizing the knowledge and research trends. The efficacy of berberine in breast and colon cancers seems to be the most promising aspect. Many papers focus on novel therapeutic strategies based on new formulations or search for new active derivatives. The activity of berberine is very important as regards sensitization and support of anticancer therapy in combination with well-known but in some cases inefficient therapeutics. Currently, the compound is being assessed in many important clinical trials and is one of the most promising and intensively examined natural agents.
  • 1.7K
  • 23 Nov 2020
Topic Review
Alkaloids and Their General Applications
Alkaloids are organic chemical compounds with a cyclic ring structure containing one or more basic nitrogen atoms. They are widely distributed in nature and are found as naturally occurring secondary metabolites in both plants and animals.
  • 1.7K
  • 11 Aug 2023
Topic Review
Inhibitors Targeting the 80S ribosome
Protein biosynthesis is a vital process for all kingdoms of life. The ribosome is the massive ribonucleoprotein machinery that reads the genetic code, in the form of messenger RNA (mRNA), to produce proteins. The mechanism of translation is tightly regulated to ensure that cell growth is well sustained. In bacteria, the ribosome is a major target of inhibitors, as demonstrated by the high number of small molecules identified to bind to it. In eukaryotes, the design of ribosome inhibitors may be used as a therapy to treat cancer cells, which exhibit higher proliferation rates compared to healthy ones. 
  • 1.7K
  • 28 Sep 2021
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