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Cancer of Unknown Primary: Challenges and Progress in Clinical Management.

Distant metastases are the main cause of cancer-related deaths in patients with advanced tumors. A standard diagnostic workup usually contains the identification of the tissue-of-origin of metastatic tumors, although under certain circumstances, it remains elusive. This disease setting is defined as cancer of unknown primary (CUP). Accounting for approximately 3-5% of all cancer diagnoses, CUPs are characterized by an aggressive clinical behavior and represent a real therapeutic challenge. The lack of determination of a tissue of origin precludes CUP patients from specific evidence-based thera

Bortezomib treatment produces nocifensive behavior and changes in the expression of TRPV1, CGRP, and substance P in the rat DRG, spinal cord, and sciatic nerve.

To investigate neurochemical changes associated with bortezomib-induced painful peripheral neuropathy (PN), we examined the effects of a single-dose intravenous administration of bortezomib and a well-established "chronic" schedule in a rat model of bortezomib-induced PN. The TRPV1 channel and sensory neuropeptides CGRP and substance P (SP) were studied in L4-L5 dorsal root ganglia (DRGs), spinal cord, and sciatic nerve. Behavioral measures, performed at the end of the chronic bortezomib treatment, confirmed a reduction of mechanical nociceptive threshold, whereas no difference occurred in the

P941 – P1197

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Exploring microRNA targeting as a promising approach for solid tumor treatment.

The discovery of microRNAs (miRNAs) and their pivotal role in gene regulation has opened up new avenues for innovative cancer treatments. Recent years have witnessed extensive research into the intricate mechanisms of miRNAs and their impact on solid tumors. These small non-coding RNA molecules are central to gene regulation and are frequently dysregulated in various cancers, particularly solid tumors. Dysregulation of specific miRNAs can initiate, progress, and metastasize tumors, making them appealing targets in cancer therapy. This article explores recent studies on identifying specific miR

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… First, miRNA genes are transcribed by RNA polymerase II or III, producing a long primary transcript called pri-miRNA ( 27 ). This pri-miRNA features a 5’ cap and a poly-A tail, forming a structured molecule. …

Sp3 улучшила экспериментальный аутоиммунный энцефаломиэлит, спровоцировав Socs3 в клетках Th17.

ВВЕДЕНИЕ: Хотя считается, что хронические подстрекательские и дегенеративные заболевания центральной нервной системы поддерживаются аутоиммунными клетками ТТ17, основополагающие механизмы остаются в основном неисследованными. Недавние исследования и наши исследования показали, что Sp3 был заблокирован в нескольких склерозах (MS) и экспериментальном аутоиммунном энцефаломиелите (EAE). Вместе с тем остается неясным, почему в нем ничего не говорится и как он регулирует дифференциацию клеток TH17 в MS. ЦЕЛИ: Данное исследование было направлено на изучение воздействия Сп3 на ТХ17 в клетках EAE и ле

Ribosomal rodeo: wrangling translational machinery in gynecologic tumors.

Gynecologic cancers are a significant cause of morbidity and mortality among women worldwide. Despite advancements in diagnosis and treatment, the molecular mechanisms underlying the development and progression of these cancers remain poorly understood. Recent studies have implicated translational machinery (ribosomal proteins (RPs) and translation factors (TFs)) as potential drivers of oncogenic processes in various cancer types, including gynecologic cancers. RPs are essential components of the ribosome, which is responsible for protein synthesis. In this review paper, we aim to explore the

MicroRNAs in Pancreatic Cancer: biomarkers, prognostic, and therapeutic modulators.

A severe lack of early diagnosis coupled with resistance to most available therapeutic options renders pancreatic cancer as a major clinical concern. The limited efficacy of current treatments necessitates the development of novel therapeutic strategies that are based on an understanding of the molecular mechanisms involved in pancreatic cancer progression. MicroRNAs (miRNAs) are non-coding small RNAs that regulate the expression of multiple proteins in the post-translation process and thus have promise as biomarkers, prognostic agents, and as advanced pancreatic therapies. Profiling of deregu

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… The biogenesis of miRNAs commences in the nucleus where the RNA polymerase II transcribes the genetic sequence encoding the miRNA to produce a primary miRNA hairpin (pri-miRNA) which is capped, polyadenylated and has a stem-loop structure. … The biogenesis of miRNAs commences in the nucleus where the RNA polymerase II transcribes the genetic sequence encoding the miRNA to produce a primary miRNA hairpin (pri-miRNA) which is capped, polyadenylated and has a stem-loop structure. …

Potential Molecular Targeted Therapy for Unresectable Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is one of the most prevalent and lethal cancers, representing a serious worldwide health concern. The recurrence incidence of hepatocellular carcinoma (HCC) following surgery or ablation is as high as 70%. Thus, the clinical applicability of standard surgery and other locoregional therapy to improve the outcomes of advanced HCC is restricted and far from ideal. The registered trials did not identify a treatment that prolonged recurrence-free survival, the primary outcome of the majority of research. Several investigator-initiated trials have demonstrated that var

Silencing of SPARC represses heterotopic ossification via inhibition of the MAPK signaling pathway.

Heterotopic ossification (HO), the pathologic formation of extraskeletal bone, can be disabling and lethal. However, the underlying molecular mechanisms were largely unknown. The present study aimed to clarify the involvement of secreted protein acidic and rich in cysteine (SPARC) and the underlying mechanism in rat model of HO. The mechanistic investigation on roles of SPARC in HO was examined through gain- and loss-of-function approaches of SPARC, with alkaline-phosphatase (ALP) activity, mineralized nodules, and osteocalcin (OCN) content measured. To further confirm the regulatory role of S

Genome Editing Approaches with CRISPR/Cas9 for Cancer Treatment: Critical Appraisal of Preclinical and Clinical Utility, Challenges, and Future Research.

The increasing burden on human malignant diseases became a major concern for healthcare practitioners, that must deal with tumor relapse and the inability to efficiently treat metastasis, in addition to side effects. Throughout the decades, many therapeutic strategies have been employed to improve the clinical outcomes of cancer patients and great efforts have been made to develop more efficient and targeted medicines. The malignant cell is characterized by genetic and epigenetic modifications, therefore targeting those specific drivers of carcinogenesis is highly desirable. Among the genome e

MicroRNA in cancer therapy: breakthroughs and challenges in early clinical applications.

MicroRNAs (miRNAs) have emerged as pivotal regulators in cancer biology, influencing tumorigenesis, progression, and resistance to therapy. Their ability to modulate multiple oncogenic and tumor-suppressive pathways positions them as promising therapeutic tools or targets. This review examines the dual role of miRNAs in solid and hematological malignancies, starting from their dysregulation in various cancer types. Therapeutic approaches, including miRNA replacement and inhibition strategies, are discussed alongside innovative delivery systems such as lipid nanoparticles and exosomes. Despite

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… Fig. 1 miRNA Biogenesis and Its Potential as a Therapeutic Target in Cancer. miRNAs biogenesis is a multi-step process that begins in the nucleus where are transcribed as pri-miRNAs by RNA polymerase II. … polymerase II. …

Всеобъемлющий анализ SOX7 дает новое представление о его роли опухоля и его целевых генах с терапевтическими последствиями в множестве миеломы.

Множественная миелома (ММ) — неизлечимая гематология. SOX7, расположенное в области 8p23.1 в MM, предлагается действовать в качестве ограничителя опухоли. Мы описали SOX7 с помощью генетического, эпигенетического и функционального анализа в линиях клеток MM. SOX7 часто замолчали из-за исключения и/или содействия гиперметилированию. Эктомическое выражение SOX7 в KMS-18 и MM.1S привело к постепенному снижению числа камер, передаваемых SOX7, и вызвало арест и/или апоптоз в клеточном цикле G1. Хотя повторное выражение SOX7 не повысило бортезомибную эффективность, лечение панхистоном деацетилазным

Targeting DNA Damage Response and Repair to Enhance Therapeutic Index in Cisplatin-Based Cancer Treatment.

Platinum-based chemotherapies, such as cisplatin, play a large role in cancer treatment. The development of resistance and treatment toxicity creates substantial barriers to disease control, yet. To enhance the therapeutic index of cisplatin-based chemotherapy, it is imperative to circumvent resistance and toxicity while optimizing tumor sensitization. One of the primary mechanisms by which cancer cells develop resistance to cisplatin is through upregulation of DNA repair pathways. In this review, we discuss the DNA damage response in the context of cisplatin-induced DNA damage. We describe th

Keyword Index for Volume 98

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Integrative meta-analysis identifies microRNA-regulated networks in infantile hemangioma.

BackgroundHemangioma is a common benign tumor in the childhood; however our knowledge about the molecular mechanisms of hemangioma development and progression are still limited. Currently, microRNAs (miRNAs) have been shown as gene expression regulators with an important role in disease pathogenesis. Our goals were to identify miRNA-mRNA expression networks associated with infantile hemangioma.MethodsWe performed a meta-analysis of previously published gene expression datasets including 98 hemangioma samples. Deregulated genes were further used to identify microRNAs as potential regulators of

Identification of Potential Key Genes and Regulatory Markers in Essential Thrombocythemia Through Integrated Bioinformatics Analysis and Clinical Validation.

IntroductionEssential thrombocytosis (ET) is a group of myeloproliferative neoplasms characterized by abnormal proliferation of platelet and megakaryocytes. Research on potential key genes and novel regulatory markers in essential thrombocythemia (ET) is still limited.MethodsDownloading array profiles from the Gene Expression Omnibus database, we identified the differentially expressed genes (DEGs) through comprehensive bioinformatic analysis. GO, and REACTOME pathway enrichment analysis was used to predict the potential functions of DEGs. Besides, constructing a protein-protein interaction (P

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… Regarding molecular function (MF), the DEGs are mainly enriched in RNA polymerase II-specific DNA-binding transcription factor binding and DNA-binding transcription factor binding ( Table 2 , Figure 2C ). … polymerase II-specific DNA-binding transcription factor binding | 7/57 | 2.89E-05 | IFI27/FHL2/PRKCB/ACTB/ LEF1/ RBL2/STAT1 MF | DNA-binding transcription factor binding | 7/57 | 0.000128279 | IFI27/FHL2/PRKCB/ACTB/ LEF1/RBL2/STAT1 Figure 2 GO term enrichment analysis of DEGs. ( A ) Biological process …

Митохондриальная ДНК (mtDNA) в качестве жидкого биомаркера в нейродегенеративных расстройствах: систематический обзор.

ИСТОРИЯ ВОПРОСА: В ряде исследований была проведена оценка периферийных и цереброспинных жидкостей (CSF) mtDNA как предполагаемого биомаркера нейродегенеративных заболеваний, что зачастую приводит к непоследовательным выводам. Мы систематически анализировали текущие данные, позволяющие оценить уровни крови и CSF mtDNA и возможное бремя в болезни Паркинсона (PD), болезни Альцгеймера (ALS) и амиотропическом боковом склерозе (ALS). Множественный склероз (MS) был также включен в качестве парадигмы хронического нейроинфламмации под воздействием нейродегенерации. МЕТОДЫ: Медлин, Эмбаза, Скопус и веб

Identification and validation of CKAP2 as a novel biomarker in the development and progression of rheumatoid arthritis.

BACKGROUND: Rheumatoid arthritis (RA) is a common chronic joint disease. However, many patients exhibit inadequate responses to treatment due to disease heterogeneity. Identifying novel biomarkers for RA is crucial for advancing molecular diagnosis and identifying potential therapeutic targets. METHODS: Synovial tissue transcriptome data from RA patients and healthy controls were obtained from the GEO database. Differentially expressed gene (DEG) analysis, functional enrichment analysis, and weighted gene co-expression network analysis (WGCNA) identified key gene modules in RA. Machine learni

Molecularly Targeted Therapies in Oncology: Mechanisms, Resistance, and Combination Strategies.

Targeted therapies are reshaping oncology by enabling treatment selection based on actionable molecular alterations, improving precision, and reducing unnecessary toxicity. This review provides an up-to-date overview of current targeted treatment modalities and the medicinal chemistry principles that support their discovery and optimization. We synthesize evidence on small-molecule and biologic strategies spanning receptor and non-receptor kinases and their major signaling axes (PI3K-AKT-mTOR and RAS-RAF-MEK-ERK), apoptosis regulation (BCL-2 family), DNA repair via poly(ADP-ribose) polymerase

Chemistry and Pharmacology of Fluorinated Drugs Approved by the FDA (2016-2022).

Fluorine is characterized by high electronegativity and small atomic size, which provide this molecule with the unique property of augmenting the potency, selectivity, metabolic stability, and pharmacokinetics of drugs. Fluorine (F) substitution has been extensively explored in drug research as a means of improving biological activity and enhancing chemical or metabolic stability. Selective F substitution onto a therapeutic or diagnostic drug candidate can enhance several pharmacokinetic and physicochemical properties such as metabolic stability and membrane permeation. The increased binding a