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Clinical Implementation of Integrated Genomic Profiling in Patients with Advanced Cancers.

DNA focused panel sequencing has been rapidly adopted to assess therapeutic targets in advanced/refractory cancer. Integrated Genomic Profiling (IGP) utilising DNA/RNA with tumour/normal comparisons in a Clinical Laboratory Improvement Amendments (CLIA) compliant setting enables a single assay to provide: therapeutic target prioritisation, novel target discovery/application and comprehensive germline assessment. A prospective study in 35 advanced/refractory cancer patients was conducted using CLIA-compliant IGP. Feasibility was assessed by estimating time to results (TTR), prioritising/assigni

Viral Vector-Based Melanoma Gene Therapy.

Gene therapy applications of oncolytic viruses represent an attractive alternative for cancer treatment. A broad range of oncolytic viruses, including adenoviruses, adeno-associated viruses, alphaviruses, herpes simplex viruses, retroviruses, lentiviruses, rhabdoviruses, reoviruses, measles virus, Newcastle disease virus, picornaviruses and poxviruses, have been used in diverse preclinical and clinical studies for the treatment of various diseases, including colon, head-and-neck, prostate and breast cancer as well as squamous cell carcinoma and glioma. The majority of studies have focused on i

Establishment of a Temperature-Sensitive Model of Oncogene-Induced Senescence in Angiosarcoma Cells.

: Lesions with driver mutations, including atypical nevi and seborrheic keratoses, are very common in dermatology, and are prone to senescence. The molecular events that prevent senescent lesions from becoming malignant are not well understood. We have developed a model of vascular proliferation using a temperaturesensitive, large T antigen and oncogenic HRas. By elevating the temperature to 39 °C, we can turn off large T antigen and study the molecular events in cells with the Ras driver mutation. To assess the signaling events associated with the switch from a proliferative to a nonprolifera

Tumor biomarkers for diagnosis, prognosis and targeted therapy.

Tumor biomarkers, the substances which are produced by tumors or the body's responses to tumors during tumorigenesis and progression, have been demonstrated to possess critical and encouraging value in screening and early diagnosis, prognosis prediction, recurrence detection, and therapeutic efficacy monitoring of cancers. Over the past decades, continuous progress has been made in exploring and discovering novel, sensitive, specific, and accurate tumor biomarkers, which has significantly promoted personalized medicine and improved the outcomes of cancer patients, especially advances in molecu

Abscopal Effect in Radiation Therapy: The Immune Mechanisms and Clinical Advances.

The abscopal effect is a systemic antitumor response to localized radiotherapy (RT) that has emerged as a central focus in the era of immunotherapy. Clinical evidence demonstrates that local RT can induce regression of distant, nonirradiated metastases, including cases of complete remission. However, the effect remains unpredictable, with marked variation in clinical outcomes ranging from complete regression to paradoxical progression. The mechanistic basis for this heterogeneity and optimal strategies to enhance abscopal effects remain incompletely understood. This review synthesizes current

Diagnostic and prognostic values of integrin α subfamily mRNA expression in colon adenocarcinoma.

The integrin α (ITGA) subfamily genes play a fundamental role in various cancers. However, the potential mechanism and application values of ITGA genes in colon adenocarcinoma (COAD) remain elusive. The present study investigated the significance of the expression of ITGA genes in COAD from the perspective of diagnosis and prognosis. A COAD RNA‑sequencing dataset was obtained from The Cancer Genome Atlas. The present study investigated the biological function of the ITGA subfamily genes through bioinformatics analysis. Reverse transcription‑quantitative polymerase chain reaction was applied to

MicroRNA‑145 promotes the apoptosis of leukemic stem cells and enhances drug‑resistant K562/ADM cell sensitivity to adriamycin via the regulation of ABCE1.

Leukemia is a type of cancer which originates in blood‑forming tissues. MicroRNAs (miRNAs or miRs) have been shown to be involved leukemogenesis. In the present study, following the gain‑ and loss‑function of miR‑145 and ATP‑binding cassette sub‑family E member 1 (ABCE1) in K562 cells and K562 adriamycin‑resistant cells (K562/ADM cells), the levels of multidrug resistance protein 1 (MRP1) and P‑glycoprotein (P‑gp) were measured. The viability of the K562 cells and K562/ADM cells treated with various concentrations of ADM, and cell sensitivity to ADM were measured. The apoptosis of stem cells w

The KISS1 Receptor as an In Vivo Microenvironment Imaging Biomarker of Multiple Myeloma Bone Disease.

Multiple myeloma is one of the most common hematological diseases and is characterized by an aberrant proliferation of plasma cells within the bone marrow. As a result of crosstalk between cancer cells and the bone microenvironment, bone homeostasis is disrupted leading to osteolytic lesions and poor prognosis. Current diagnostic strategies for myeloma typically rely on detection of excess monoclonal immunoglobulins or light chains in the urine or serum. However, these strategies fail to localize the sites of malignancies. In this study we sought to identify novel biomarkers of myeloma bone di

Drug Repurposing for Cancer Treatment: A Comprehensive Review.

Cancer ranks among the primary contributors to global mortality. In 2022, the global incidence of new cancer cases reached about 20 million, while the number of cancer-related fatalities reached 9.7 million. In Saudi Arabia, there were 13,399 deaths caused by cancer and 28,113 newly diagnosed cases of cancer. Drug repurposing is a drug discovery strategy that has gained special attention and implementation to enhance the process of drug development due to its time- and money-saving effect. It involves repositioning existing medications to new clinical applications. Cancer treatment is a therap

Abstracts cont.

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Oncolytic viruses on the cusp of success?: proceedings of the 9th International Conference on Oncolytic Virus Therapeutics

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The Landscape of lncRNAs in Multiple Myeloma: Implications in the "Hallmarks of Cancer", Clinical Perspectives and Therapeutic Opportunities.

Long non-coding RNAs (lncRNAs) are transcripts longer than 200 nucleotides that are not translated into proteins. Nowadays, lncRNAs are gaining importance as key regulators of gene expression and, consequently, of several biological functions in physiological and pathological conditions, including cancer. Here, we point out the role of lncRNAs in the pathogenesis of multiple myeloma (MM). We focus on their ability to regulate the biological processes identified as "hallmarks of cancer" that enable malignant cell transformation, early tumor onset and progression. The aberrant expression of lncR

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… LncRNAs Biogenesis and Functions The majority of lncRNAs are transcribed by RNA Polymerase II from several genome loci leading to different classes that are grouped based on their orientation and localization in the genome as: ( i ) sense lncRNAs, transcribed in the sense of coding genes (5′-3′); ( …

Gene expression signatures that predict radiation exposure in mice and humans.

BackgroundThe capacity to assess environmental inputs to biological phenotypes is limited by methods that can accurately and quantitatively measure these contributions. One such example can be seen in the context of exposure to ionizing radiation.Methods and findingsWe have made use of gene expression analysis of peripheral blood (PB) mononuclear cells to develop expression profiles that accurately reflect prior radiation exposure. We demonstrate that expression profiles can be developed that not only predict radiation exposure in mice but also distinguish the level of radiation exposure, rang

A Rare and Fatal Case of Hemophagocytic Lymphohistiocytosis Associated with Sarcoidosis.

BACKGROUND Sarcoidosis is a systemic inflammatory disorder characterized by a classic pathologic feature of non-caseating granulomas involving any organ system. Hemophagocytic lymphohistiocytosis (HLH) is a catastrophic cytokine surge characterized by dysregulation of the macrophage response, which can be rapidly fatal. Recognition of HLH has been increasing over the past decade. HLH can present with features of sepsis that can make the diagnosis challenging and requires high clinical suspicion. CASE REPORT We report a case of a 48-year-old African American male with a past medical history of

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… EIciRNAs and U1 small nuclear ribonucleic proteins (U1 snRNPs) are co-localized to the promoter of the parental gene and promote transcription of the parental gene with the participation of RNA polymerase II. 4 Results of the publication search We retrieved 197 publications from Pubmed, CNKI, Web of …

The Fibronectin Expression Determines the Distinct Progressions of Malignant Gliomas via Transforming Growth Factor-Beta Pathway.

Due to the increasing incidence of malignant gliomas, particularly glioblastoma multiforme (GBM), a simple and reliable GBM diagnosis is needed to screen early the death-threaten patients. This study aimed to identify a protein that can be used to discriminate GBM from low-grade astrocytoma and elucidate further that it has a functional role during malignant glioma progressions. To identify proteins that display low or no expression in low-grade astrocytoma but elevated levels in GBM, glycoprotein fibronectin (FN) was particularly examined according to the mining of the Human Protein Atlas. We

Circular RNA as a Novel Biomarker for Diagnosis and Prognosis and Potential Therapeutic Targets in Multiple Myeloma.

Circular RNAs (circRNAs) are a novel type of covalently closed RNAs involved in several physiological and pathological processes. They display tissue-specific expression and are constant, abundant, and highly conserved, making them perfect markers for diagnosis and prognosis. Several studies have proposed that circRNAs are also differentially produced in malignancies where they have oncogenic effects. Furthermore, circRNAs affecting microRNAs modify the expression profile of several transcription factors which play essential roles in tumors. CircRNAs within the hematopoietic compartment were i

Vision of Life's Code: Molecular Probe Nanoarchitectonics for Deep RNA/DNA Illumination.

Visualization of RNA and DNA provides a window of opportunity for the early detection of multiple diseases and approaches to manipulate them before any pathological processes occur. However, current imaging systems often fail to meet these demands due to the need for multiple RNA and DNA chemical probes, which increases experimental complexity, reduces awareness of false positives, and limits imaging accuracy in complex biosystems. In this work, we identify the key challenges associated with using multiple probes for RNA and DNA imaging and analyze the mechanisms and performance of existing im

Targeting B Cell Maturation Antigen (BCMA) in Multiple Myeloma: Potential Uses of BCMA-Based Immunotherapy.

The approval of the first two monoclonal antibodies targeting CD38 (daratumumab) and SLAMF7 (elotuzumab) in late 2015 for treating relapsed and refractory multiple myeloma (RRMM) was a critical advance for immunotherapies for multiple myeloma (MM). Importantly, the outcome of patients continues to improve with the incorporation of this new class of agents with current MM therapies. However, both antigens are also expressed on other normal tissues including hematopoietic lineages and immune effector cells, which may limit their long-term clinical use. B cell maturation antigen (BCMA), a transme

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… HDP-101 HDP-1, an antibody-targeted amanitin conjugate, is an anti-BCMA ADC with a novel payload amanitin, which binds to the RNA polymerase II in eukaryotic cells and inhibits cellular transcription at very low concentrations ( 108 ). … Amanitin greatly reduces the rate of transcription by RNA polymerase II ternary complexes but fails to inhibit some transcript cleavage modes. J Biol Chem (1996) 271(35):21549–58. 10.1074/jbc.271.35.21549 109. Bhakta S, Raab H, Junutula JR. …

The next frontier in antibody-drug conjugates: challenges and opportunities in cancer and autoimmune therapy.

Antibody-Drug Conjugates (ADCs) have achieved significant success in cancer therapy by combining the targeting specificity of monoclonal antibodies with cytotoxic payloads. However, the concomitant issue of drug resistance has become increasingly prominent, with primary mechanisms including alterations in target antigen expression, impaired drug transport, and inhibition of cell death pathways. ADCs have also shown emerging therapeutic potential in the treatment of autoimmune diseases; for instance, ABBV-3373 has achieved initial success in this area, yet it also faces unique challenges such a

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… Currently, the world’s first dual-payload ADC to enter clinical trials is KH815 (an anti-TROP2 ADC) developed by China’s Kanghong Pharma ( NCT06885645 ): this drug links two types of toxins, a topoisomerase I inhibitor and an RNA polymerase II inhibitor, to enhance antitumor efficacy by inducing DNA … polymerase II; Topo-I: topoisomerase I; TROP2: trophoblast cell-surface antigen 2. …

Acute myeloid leukemia: from NGS, through scRNA-seq, to CAR-T. dissect cancer heterogeneity and tailor the treatment.

Acute myeloid leukemia (AML) is a malignant blood cancer with marked cellular heterogeneity due to altered maturation and differentiation of myeloid blasts, the possible causes of which are transcriptional or epigenetic alterations, impaired apoptosis, and excessive cell proliferation. This neoplasm has a high rate of resistance to anticancer therapies and thus a high risk of relapse and mortality because of both the biological diversity of the patient and intratumoral heterogeneity due to the acquisition of new somatic changes. For more than 40 years, the old gold standard "one size fits all"