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Topic Review
Chemistry and Radiochemistry of DOTAZOL
Bisphosphonates are therapeutic agents that have been used for almost five decades in the treatment of various bone diseases, such as osteoporosis, Paget disease and prevention of osseous complications in cancer patients. In nuclear medicine, simple bisphosphonates such as 99mTc-radiolabelled oxidronate and medronate remain first-line bone scintigraphic imaging agents for both oncology and non-oncology indications. In addition, bifunctional bisphosphonates such as DOTAZOL can be tagged with radiometals for theranostic applications.
  • 903
  • 05 Jan 2024
Topic Review
CNNs in lymph node metastasis
Deep learning models have potential to improve performance of automated computer-assisted diagnosis tools in digital histopathology and reduce subjectivity. The main objective of this study was to further improve diagnostic potential of convolutional neural networks (CNNs) in detection of lymph node metastasis in breast cancer patients by integrative augmentation of input images with multiple segmentation channels. For this retrospective study, we used the PatchCamelyon dataset, consisting of 327,680 histopathology images of lymph node sections from breast cancer. Images had labels for the presence or absence of metastatic tissue. In addition, we used four separate histopathology datasets with annotations for nucleus, mitosis, tubule, and epithelium to train four instances of U-net. Then our baseline model was trained with and without additional segmentation channels and their performances were compared. Integrated gradient was used to visualize model attribution. The model trained with concatenation/integration of original input plus four additional segmentation channels, which we refer to as ConcatNet, was superior (AUC 0.924) compared to baseline with or without augmentations (AUC 0.854; 0.884). Baseline model trained with one additional segmentation channel showed intermediate performance (AUC 0.870-0.895). ConcatNet had sensitivity of 82.0% and specificity of 87.8%, which was an improvement in performance over the baseline (sensitivity of 74.6%; specificity of 80.4%). Integrated gradients showed that models trained with additional segmentation channels had improved focus on particular areas of the image containing aberrant cells. Augmenting images with additional segmentation channels improved baseline model performance as well as its ability to focus on discrete areas of the image.
  • 902
  • 19 Oct 2020
Topic Review
Radiosensitizing Hypoxic Tumour Cells
One of the most difficult barriers encountered when treating the majority of solid tumours is attributed to the scattered microregions within the tumour characterized by the lack of oxygen. This is known as tumour hypoxia. The lack of oxygen supply results in hypoxic microregions scattered throughout the tumour relative to normal tissue. The hypoxic environments within tumours create several cancer treatment barriers. Most notably, all hypoxic cells are resistant to ionizing radiation (IR). The mechanism by which radiation is able to eradicate tumour cells by damaging DNA, resulting in apoptosis and cell death, occurs through the production of reactive oxygen species (ROS). However, due to the limited oxygen availability within hypoxic tumour microenvironments, this impedes the efficacy of radiotherapy. Furthermore, normal tissues are unable to withstand increased doses of radiation that compensate for tumour hypoxia. Methods targeting tumour hypoxia through radiosensitizing hypoxic cells include hyperbaric oxygen, hypoxic cell radiosensitizers, hypoxic cytotoxins, and tumour metabolism. As research continues to elucidate the relationship between tumour hypoxia and radiotherapy, novel approaches have been developed.
  • 902
  • 06 Sep 2021
Topic Review
Cancer Stem Cells and Radioresistance
The current preclinical and clinical findings demonstrate that, in addition to the conventional clinical and pathological indicators that have a prognostic value in radiation oncology, the number of cancer stem cells (CSCs) and their inherent radioresistance are important parameters for local control after radiotherapy.
  • 902
  • 08 Sep 2021
Topic Review
Allogeneic Hematopoietic Cell Transplantation
Allogeneic hematopoietic cell transplantation (alloHCT) represents a treatment option for multiple myeloma (MM) patients. As shown in several studies, alloHCT is highly effective, but it is hampered by a high toxicity, mainly related to the graft-versus-host disease (GVHD), a complex immunological reaction ascribable to the donor’s immune system. The morbidity and mortality associated with GVHD can weaken the benefits of this procedure. On the other side, the high therapeutic potential of alloHCT is also related to the donor’s immune system, through immunological activity known as the graft-versus-myeloma effect.
  • 901
  • 09 Nov 2020
Topic Review
STAT6
Inflammation is the main driver of tumor initiation and progression in colitis-associated colorectal cancer (CAC). Recent findings have indicated that the signal transducer and activator of transcription 6 (STAT6) plays a fundamental role in the early stages of CAC, and STAT6 knockout (STAT6−/−) mice are highly resistant to CAC development. Regulatory T (Treg) cells play a major role in coordinating immunomodulation in cancer; however, the role of STAT6 in the induction and function of Treg cells is poorly understood. To clarify the contribution of STAT6 to CAC, STAT6−/− and wild type (WT) mice were subjected to an AOM/DSS regimen, and the frequency of peripheral and local Treg cells was determined during the progression of CAC. When STAT6 was lacking, a remarkable reduction in tumor growth was observed, which was associated with decreased inflammation and an increased number of CD4+CD25+Foxp3+ cells. STAT6 has a direct role in the induction and function of Treg cells during CAC development.  
  • 901
  • 22 Sep 2021
Topic Review
Precision Medicine for Cancer
The diagnosis and treatment of diseases such as cancer is becoming more accurate and specialized with the advent of precision medicine techniques, research and treatments. Reaching down to the cellular and even sub-cellular level, diagnostic tests can pinpoint specific, individual information from each patient, and guide providers to a more accurate plan of treatment. With this advanced knowledge, researchers and providers can better gauge the effectiveness of drugs, radiation, and other therapies, which is bound to lead to a more accurate, if not more positive, prognosis. As precision medicine becomes more established, new techniques, equipment, materials and testing methods will be required. Herein, we will examine the recent innovations in assays, devices and software, along with next generation sequencing in genomics diagnostics which are in use or are being developed for personalized medicine. So as to avoid duplication and produce the fullest possible benefit, all involved must be strongly encouraged to collaborate, across national borders, public and private sectors, science, medicine and academia alike. In this paper we will offer recommendations for tools, research and development, along with ideas for implementation. We plan to begin with discussion of the lessons learned to date, and the current research on pharmacogenomics. Given the steady stream of advances in imaging mass spectrometry and nanoLC-MS/MS, and use of genomic, proteomic and metabolomics biomarkers to distinguish healthy tissue from diseased cells, there is great potential to utilize pharmacogenomics to tailor a drug or drugs to a particular cohort of patients. Such efforts very well may bring increased hope for small groups of non-responders and those who have demonstrated adverse reactions to current treatments.
  • 900
  • 15 Feb 2021
Topic Review
Gut Microbiota and Immunotherapy
Gut microbiota can have opposing functions from pro-tumorigenic to anti-tumorigenic effects. Increasing preclinical and clinical evidence suggests that the intestinal microbiota affects cancer patients’ response to immune checkpoint inhibitors (ICIs) immunotherapy, such as anti-programmed cell death protein 1 (PD-1) and its ligand (PD-L1) and anti-cytotoxic T lymphocyte-associated protein 4 (CTLA-4). Microbiota-induced inflammation possibly contributes to tumor growth and cancer development. Microbiota-derived metabolites can also be converted to carcinogenic agents related to genetic mutations and DNA damage in organs such as the colon. However, other attributes of microbiota, such as greater diversity and specific bacterial species and their metabolites, are linked to better clinical outcomes and potentially improved anti-tumor immunity. In addition, the intratumoral microbial composition strongly affects T-cell-mediated cytotoxicity and anti-tumor immune surveillance, adding more complexity to the cancer-microbiome-immune axis.
  • 900
  • 26 Aug 2022
Topic Review
Resveratrol Encapsulation as an Anticancer Agent
Resveratrol is a polyphenolic compound that has gained considerable attention in the past decade due to its multifaceted therapeutic potential, including anti-inflammatory and anticancer properties. However, its anticancer efficacy is impeded by low water solubility, dose-limiting toxicity, low bioavailability, and rapid hepatic metabolism. To overcome these hurdles, various nanoparticles such as organic and inorganic nanoparticles, liposomes, polymeric nanoparticles, dendrimers, solid lipid nanoparticles, gold nanoparticles, zinc oxide nanoparticles, zeolitic imidazolate frameworks, carbon nanotubes, bioactive glass nanoparticles, and mesoporous nanoparticles were employed to deliver resveratrol, enhancing its water solubility, bioavailability, and efficacy against various types of cancer.
  • 900
  • 22 Jan 2024
Topic Review
Histone Deacetylases as Tumor Suppressors
Histone deacetylases (HDACs) deacetylate their targets, which leads to either the upregulation or downregulation of proteins involved in the regulation of cell cycle and apoptosis, ultimately influencing tumor growth, invasion, and drug resistance. 
  • 899
  • 26 Apr 2022
Topic Review
Hyperglycemia and endometrial cancer risk
Endometrial cancer is one of the most common cancers in women worldwide and its incidence is increasing. Epidemiological evidence shows a strong association between endometrial cancer and obesity, and multiple mechanisms linking obesity and cancer progression have been described. However, it remains unclear which factors are the main drivers of endometrial cancer development. Hyperglycemia and type 2 diabetes mellitus are common co-morbidities of obesity, and there is evidence that hyperglycemia is a risk factor for endometrial cancer independent of obesity. This review will discuss studies that have investigated the links between hyperglycemia and endometrial cancer risk.
  • 899
  • 03 Nov 2020
Topic Review
Genomic Alterations in ALL
Acute lymphoblastic leukemia (ALL) is the most successful paradigm of how risk-adapted therapy and detailed understanding of the genetic alterations driving leukemogenesis and therapeutic response may dramatically improve treatment outcomes, with cure rates now exceeding 90% in children. 
  • 898
  • 09 Sep 2021
Topic Review
Orofacial Cancers
Orofacial cancers result in facial deformities and impairment of vital functions and are often lethal. These aggressive solid tumors exhibit great heterogeneity between them and show distinct and exclusive molecular alterations that deregulate the function of important signaling pathways. The Notch signaling pathway is involved in the initiation and development of orofacial cancers. Increasing evidence suggests that Notch molecules may have a dual function in cancer, acting either as oncogenes or tumor suppressor genes. Crosstalk between Notch and other signaling pathways provides a critical multidirectional control in these cancers. Protein phosphorylation is activated in cancers and therefore novel drugs inhibiting phosphorylation events (kinase inhibitors) are increasingly used in the treatment of cancers. Another pharmacological strategy is the selective targeting of Notch signaling in order to eliminate the cancer stem cells using monoclonal antibodies against specific regions of the Notch molecules. Organoids, “organ-on-a-chip” devices and single-cell genomic analyses could be used for further investigations and preclinical studies in orofacial cancers. Organoids can be used to study complex interactions between the various cells lines in orofacial cancers, as well as for the preclinical screening of novel drugs. Microfluidic culture systems, also called “organs-on-chips”, can be used to model cancer cell behavior within orofacial tissues and their environment. These chips also enable to vary drug delivery and composition in a controlled manner in order to study cancer tissue responses to various pharmaceutical anticancer products. Single-cell RNA-seq analyses allow exploring the genetic and functional heterogeneity of orofacial cancers at a cellular resolution, thus revealing new insights into tumor composition and drug resistance. These important technological developments and the innovative therapeutic strategies demonstrate significant promise and generate enthusiasm and optimism within the oncology community.
  • 898
  • 28 Oct 2020
Topic Review
Wnt Signaling in Keratinocyte Carcinomas
The skin functions as a barrier between the organism and the surrounding environment. Direct exposure to external stimuli and the accumulation of genetic mutations may lead to abnormal cell growth, irreversible tissue damage and potentially favor skin malignancy. Skin homeostasis is coordinated by an intricate signaling network, and its dysregulation has been implicated in the development of skin cancers. Wnt signaling is one such regulatory pathway orchestrating skin development, homeostasis, and stem cell activation. Aberrant regulation of Wnt signaling cascades not only gives rise to tumor initiation, progression and invasion, but also maintains cancer stem cells which contribute to tumor recurrence.
  • 897
  • 22 Sep 2021
Topic Review
Chimeric RNAs and Cancer Evolution
Due to the consequences of genome instability in cancer cells, sometimes two mRNAs can be fused to generate chimeric RNAs. Several recent studies demonstrated that chimeric RNAs are significantly associated with oncogenesis and can also promote drug resistance. The generation of chimeric RNAs could allow cancer cells to switch their functionality. Therefore, chimeric RNAs are an important driver for generating the phenotypic plasticity of cancer cells and increasing their fitness in the tissue environment. Chimeric RNAs could be translated and generate new fusion or chimeric proteins that could alter the normal pathways and lead to cancer development. Chimeric RNAs could also generate long non-coding RNA (lncRNA), which could regulate cancer cell proliferation.
  • 897
  • 02 Sep 2021
Topic Review
Targeted Therapies in TNBC
Triple negative breast cancer (TNBC) constitutes the most aggressive molecular subtype among breast tumors. Despite progress on the underlying tumor biology, clinical outcomes for TNBC unfortunately remain poor. The median overall survival for patients with metastatic TNBC is approximately eighteen months. Chemotherapy is the mainstay of treatment while there is a growing body of evidence that targeted therapies may be on the horizon with poly-ADP-ribose polymerase (PARP) and immune check-point inhibitors already established in the treatment paradigm of TNBC. A large number of novel therapeutic agents are being evaluated for their efficacy in TNBC. As novel therapeutics are now incorporated into clinical practice, it is clear that tumor heterogeneity and clonal evolution can result to de novo or acquired treatment resistance. As precision medicine and next generation sequencing is part of cancer diagnostics, tailored treatment approaches based on the expression of molecular markers are currently being implemented in clinical practice and clinical trial design. 
  • 896
  • 22 Jun 2021
Topic Review
Impact of Monoclonal Antibodies in Pediatric Cancer
Monoclonal antibodies (mAbs), as the name implies, are clonal antibodies that bind to the same antigen. mAbs are broadly used as diagnostic or therapeutic tools for neoplasms, autoimmune diseases, allergic conditions, and infections.  
  • 896
  • 04 Aug 2023
Topic Review
Cryosurgery in Breast Cancer Management
Breast cancer is the most prevalent cancer and the second leading cause of death among women, primarily due to the development of deadly metastases in 25–50% of patients, resulting in an unfavorable prognosis. Consequently, there is growing interest in exploring innovative therapeutic approaches to improve clinical outcomes and enhance the quality of life for breast cancer patients.
  • 895
  • 09 Nov 2023
Topic Review
Non-Invasive Biomarkers for Immunotherapy with Hepatocellular Carcinoma
Tumor biomarkers are cellular and molecular products linked directly or indirectly to the presence of cancer cells that are an expression of the tumor’s intrinsic characteristics and can be identified, measured, and analyzed by specific tests.  Currently, there is an increasing interest in developing novel techniques to extract information on tumor biology directly from patient’s body fluids in a non-invasive way. Liquid biopsy, a non-invasive approach of tumor biomarkers detection, permits a dynamic picture of HCC’s evolution and response to therapy. 
  • 895
  • 20 Oct 2022
Topic Review
Manipulating EVs for Therapeutic Applications
Extracellular vesicles (EVs) receive special attention from clinicians due to their assumed usefulness as prognostic markers, immune modulators and physiological delivery tools. The latter application, that supports the reduction of side effects of treatment, is still fraught with many challenges, including established methods for loading EVs with selected cargo and directing them towards target cells. EVs could be loaded with selected cargo either in vitro using several physicochemical techniques, or in vivo by modification of parental cell. Otherwise, EVs may be passively supplemented with selected cargo, such as miRNAs or siRNA. Furthermore, recent findings imply that antigen-specific antibody light chains could coat the surface of EVs to increase the specificity of cell targeting. In addition, the route of EVs’ administration also determines their bioavailability and eventually induced therapeutic effect.
  • 894
  • 03 Jul 2020
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