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JAK inhibition in PD-1 immunotherapy and tumor microenvironment.

Targeting the programmed cell death 1 (PD-1)/PD-L1 axis has revolutionized cancer therapy; however, the durability of clinical responses is frequently compromised by chronic inflammation and an immunosuppressive tumor microenvironment (TME). The Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway serves as a central intracellular node integrating cytokine signals that drive these resistance mechanisms. While physiological JAK/STAT signaling is essential for antitumor immunity, its persistent aberrant activation promotes malignant progression, upregulates

Tumor cell plasticity in targeted therapy-induced resistance: mechanisms and new strategies.

Despite the success of targeted therapies in cancer treatment, therapy-induced resistance remains a major obstacle to a complete cure. Tumor cells evade treatments and relapse via phenotypic switching driven by intrinsic or induced cell plasticity. Several reversible mechanisms have been proposed to circumvent tumor cell plasticity, including epigenetic modifications, regulation of transcription factors, activation or suppression of key signaling pathways, as well as modification of the tumor environment. Epithelial-to-mesenchymal transition, tumor cell and cancer stem cell formation also serv

Influence of Hypoxia on Tumor Heterogeneity, DNA Repair, and Cancer Therapy: From Molecular Insights to Therapeutic Strategies.

Hypoxia, characterized by a reduction in tissue oxygen levels, is a hallmark of many solid tumors and affects a range of cellular processes, including DNA repair. In low-oxygen conditions, cancer cells often suppress key DNA repair pathways such as homologous recombination (HR), leading to the accumulation of DNA damage and increased genomic instability. These changes not only drive tumor progression but also contribute to resistance against conventional therapies. Hypoxia significantly reduces the effectiveness of oxygen-dependent treatments, including radiotherapy and many chemotherapeutic a

Is Curcumin the Answer to Future Chemotherapy Cocktail?

The rise in cancer cases in recent years is an alarming situation worldwide. Despite the tremendous research and invention of new cancer therapies, the clinical outcomes are not always reassuring. Cancer cells could develop several evasive mechanisms for their survivability and render therapeutic failure. The continuous use of conventional cancer therapies leads to chemoresistance, and a higher dose of treatment results in even greater toxicities among cancer patients. Therefore, the search for an alternative treatment modality is crucial to break this viscous cycle. This paper explores the su

LncRNA LGALS8-AS1 Promotes Breast Cancer Metastasis Through miR-125b-5p/SOX12 Feedback Regulatory Network.

BackgroundMetastasis is a major factor weakening the long-term survival of breast cancer patients. Increasing evidence revealed that long non-coding RNAs (lncRNAs) were involved in the occurrence and development of breast cancer. In this study, we aimed to investigate the role of LGALS8-AS1 in the metastatic progression of breast cancer cells and its potential mechanisms.ResultsThe lncRNA LGALS8-AS1 was highly expressed in breast cancer and associated with poor survival. LGALS8-AS1 functioned as an oncogenic lncRNA that promoted the metastasis of breast cancer both in vitro and in vivo. It upr

Application of Perinatal Derivatives on Oncological Preclinical Models: A Review of Animal Studies.

The increasing cancer incidence has certified oncological management as one of the most critical challenges for the coming decades. New anticancer strategies are still needed, despite the significant advances brought to the forefront in the last decades. The most recent, promising therapeutic approaches have benefitted from the application of human perinatal derivatives (PnD), biological mediators with proven benefits in several fields beyond oncology. To elucidate preclinical results and clinic outcomes achieved in the oncological field, we present a narrative review of the studies resorting

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… Chronic wound healing by amniotic membrane: TGF-β and EGF signaling modulation in re-epithelialization. Front. Bioeng. Biotechnol. 2021;9:689328. doi: 10.3389/fbioe.2021.689328. 11. Joerger-Messerli M.S., Oppliger B., Spinelli M., Thomi G., Di Salvo I., Schneider P., Schoeberlein A. …

Forkhead box F2 as a novel prognostic biomarker and potential therapeutic target in human cancers prone to bone metastasis: a meta-analysis.

ObjectiveTo undertake a systematic review and meta-analysis to evaluate the prognostic value of Forkhead box F2 (FOXF2) levels in different types of cancers prone to bone metastasis.MethodsA systematic search of publications listed in electronic databases (The Web of Science, EMBASE®, PubMed®, PMC, Science Direct and CNKI) from inception to 5 November 2020 was conducted. The hazard ratios (HRs) and 95% confidence intervals (95% CIs) were used to assess the relationship between FOXF2 levels and patient prognosis including overall survival (OS) and disease-free survival (DFS).ResultsSixteen stud

The Controversial Role of IL-33 in Lung Cancer.

Interleukin-33 (IL-33) belongs to the interleukin-1 (IL-1) family, and its structure is similar to IL-18. When cells are damaged or undergo necrosis, mature form of IL-33 is secreted as a cytokine, which can activate the immune system and provide danger signals. The IL-33/ST2 signaling pathway is composed of IL-33, suppression of tumorigenicity 2 (ST2), and IL-1 receptor accessory protein (IL-1RAcP). IL-33 has been reported to be strongly associated with lung cancer progression, and can exhibit opposite effects on lung cancer under different conditions. In this review, we have summarized the s

The Hypoxia-Retinoid Axis in Idiopathic Pulmonary Fibrosis: Multifaceted Etiology and Therapeutic Potential.

Idiopathic pulmonary fibrosis (IPF) is a progressive and lethal lung disease with limited therapeutic options. This review focuses on the role of retinoids, particularly all-trans retinoic acid (atRA), and hypoxia in the pathogenesis of IPF. Despite an established understanding of genetic and environmental factors in IPF, the interplay between retinoid signaling and the response to hypoxia remains poorly explored due to its complexity. Preclinical evidence suggests that atRA could help reduce pulmonary fibrosis by modulating TGF-β signaling pathways and epithelial-to-mesenchymal transition (EM

Targeting the Sonic Hedgehog Signaling Pathway: Review of Smoothened and GLI Inhibitors.

The sonic hedgehog (Shh) signaling pathway is a major regulator of cell differentiation, cell proliferation, and tissue polarity. Aberrant activation of the Shh pathway has been shown in a variety of human cancers, including, basal cell carcinoma, malignant gliomas, medulloblastoma, leukemias, and cancers of the breast, lung, pancreas, and prostate. Tumorigenesis, tumor progression and therapeutic response have all been shown to be impacted by the Shh signaling pathway. Downstream effectors of the Shh pathway include smoothened (SMO) and glioma-associated oncogene homolog (GLI) family of zinc

The roles of Cryptochrome-1: the circadian clock as a control point in cancer therapy.

In this review, we carefully describe the composition and operation of cryptochrome-1 (CRY1). We introduce four related signaling pathways, namely cAMP/PKA/CREB signaling way, HIFα signaling way, NF-κB signaling way, STAT3 signaling way, FOXO signaling pathway and Hedgehog (HH) signaling pathway. We also emphasize the current understanding of the complex roles CRY1 plays in the progression of various solid tumors. We propose that its function represents a novel therapeutic target that could pave the way for new cancer treatments. Additionally, we summarize three emerging therapeutic strategies

Novel therapeutic approaches for pulmonary fibrosis.

Pulmonary fibrosis represents the end stage of a number of heterogeneous conditions and is, to a greater or lesser degree, the hallmark of the interstitial lung diseases. It is characterized by the excessive deposition of extracellular matrix proteins within the pulmonary interstitium leading to the obliteration of functional alveolar units and in many cases, respiratory failure. While a small number of interstitial lung diseases have known aetiologies, most are idiopathic in nature, and of these, idiopathic pulmonary fibrosis is the most common and carries with it an appalling prognosis - med

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… Myofibroblasts in turn provoke basement membrane disruption and alveolar epithelial cell (AEC) apoptosis, perpetuating the damage and preventing appropriate re-epithelialization. … Subsequent contraction of activated fibroblasts/myofibroblasts within this matrix approximates the epithelial margins to allow re-epithelialization and wound closure. …

Spermidine/spermine N1-acetyltransferase-1 as a diagnostic biomarker in human cancer.

AimSSAT-1 is an enzyme that plays a critical role in cell growth. Amantadine, a FDA-approved antiviral drug, is a substrate for SSAT-1. The utility of amantadine as an agent to demonstrate elevated SSAT-1 activity linked to cancer was conducted.ResultsHigh levels of SSAT-1 expression were measured in tumor human cell lines, and in breast, prostate and lung tumor tissue. An increase in the urinary levels of acetylated amantadine in cancer patients was observed.ConclusionIncreases in SSAT-1 contents in tumor tissue could be of value in targeting cancers with high SSAT-1 expression for confirmati

Семья " Interleukin-17 " в области здравоохранения и иммунных заболеваний: от происхождения до клинических последствий.

Семья интерлейкин-17 является ключевой группой цитокинов и демонстрирует широкий спектр биологических функций, включая регулирование подстрекательского каскада в различных аутоиммунных и подстрекательских болезнях, таких, как множественный склероз, оптический спектр нейромилита, миастения гравис, синдром Гильен-Барре, острый распределенный энцфаломиэлит, диабет, воспалительные кожные заболевания, суставное воспаление и рак. Хотя функция семьи интерлейкин-17 привлекает все большее внимание к исследованиям на протяжении многих лет, выражение, функции и механизмы регулирования различных членов се

SETD2 and EZH2: Two epigenetic drivers of prostate cancer.

Prostate cancer is a prevalent malignancy among men, characterized by complex mechanisms underlying metastasis and treatment resistance. Epigenetic modifications play a crucial role in regulating prostate cancer progression, particularly involving histone methyltransferases such as SET-domain containing 2 (SETD2) and Enhancer of Zeste homolog 2 (EZH2). SETD2 contributes to chromatin stability by catalyzing the trimethylation of histone H3 lysine 36 (H3K36me3), and its downregulation is strongly correlated with increased invasiveness and epithelial-mesenchymal transition in prostate cancer. Con

Beyond Individual Acute Phase Protein Assessments: Introducing the Acute Phase Index (API) as a Prognostic Indicator in Dogs with Malignant Neoplasia.

Acute phase proteins (APPs) are part of the innate immune response, changing during inflammation. An Acute Phase Index (API) is a calculated value that combines multiple APPs. In human medicine, the introduction of APIs has improved outcome monitoring. In veterinary medicine, APIs have been evaluated in livestock and dogs with Leishmaniasis. This study aimed to calculate an API and evaluate its significance in cancer-bearing dogs. Sera were collected from 55 dogs, which were classified by neoplastic category and survival times (> or < than 30 and 90 days). For 32 dogs, multiple samples were av

Postbiotics as Emerging Strategy Targeting Obesity- and Aging-Related Breast Cancer-Prospects in Prophylaxis and Therapy.

Aging and obesity accompanied with hormonal disequilibrium represent critical, inter-related risk factors for breast cancer, significantly influencing disease incidence, progression, and therapeutic outcomes. This review aims to elucidate the multifaceted biological mechanisms linking obesity and aging to breast carcinogenesis, with a particular focus on the emerging therapeutic and preventive potential of postbiotics as molecules targeting cellular events important for cancer growth and responsiveness. Despite continuous advancement, breast cancer therapy still poses several challenges, such

Mutual connected IL-6, EGFR and LIN28/Let7-related mechanisms modulate PD-L1 and IGF upregulation in HNSCC using immunotherapy

The development of techniques and immunotherapies are widely applied in cancer treatment such as checkpoint inhibitors, adoptive cell therapy, and cancer vaccines apart from radiation therapy, surgery, and chemotherapy give enduring anti-tumor effects. Minority people utilize single-agent immunotherapy, and most people adopt multiple-agent immunotherapy. The difficulties are resolved by including the biomarkers to choose the non-responders’ and responders’ potentials. The possibility of the potential complications and side effects are examined to improve cancer therapy effects. The Head and Ne

Bispecific antibodies in the treatment of epithelial ovarian, endometrial, and cervical cancer: an overview of current applications, challenges, and emerging opportunities.

Gynecological cancer remains one of the leading causes of mortality worldwide. Recent advances in genomic and molecular sequencing have significantly enhanced our understanding of the biological pathways that drive tumor progression and resistance to therapy. Targeted therapies, including monoclonal antibodies (mAbs), have revolutionized cancer treatment by selectively interfering with oncogenic proteins expressed on cancer cells. However, the long-term clinical benefit is often limited due to the emergence of drug resistance, frequently mediated by compensatory signaling pathways or immune es

Evaluation of Local and Systemic Melatonin Administration on Bone Healing After Tooth Extraction in Bisphosphonate-Treated Rats.

BACKGROUND: The purpose of our study was to investigate the effects of systemic and local application of melatonin after tooth extraction in bisphosphonate applied rats, on the healing of extraction socket histopathologically and immunohistochemically. METHODS: Forty four Wistar albino rats were included in the study. Subjects were divided into 4 groups: Control (C), Bisphosphonate (BIF), Bisphosphonate + Local Melatonin (BIF + LM) and Bisphosphonate + Systemic Melatonin (BIF + SM). Zoledronic acid was applied intraperitoneally once a week from the beginning of the experiment to all the groups