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Pyoderma gangrenosum: pathogenetic mechanisms and their implications for treatment.

Pyoderma gangrenosum (PG) is a rare inflammatory skin disease belonging to the group of neutrophilic dermatoses. The pathogenesis of PG involves a predisposing genetic background that facilitates a dysregulated innate and adaptive immune response, with an imbalance between pro-inflammatory and anti-inflammatory mediators, leading to neutrophil-driven inflammatory damage. Several immunosuppressants and immunomodulatory drugs are currently available for the treatment of PG, in combination with topical therapies, wound management and pain control strategies. Systemic corticosteroids and cyclospor

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… Other medications possibly linked to PG onset or exacerbations were isotretinoin, propylthiouracil, and the tyrosine-kinase inhibitors sunitinib and gefitinib [ 15 ]. …

Polydatin: Pharmacological Mechanisms, Therapeutic Targets, Biological Activities, and Health Benefits.

Polydatin is a natural potent stilbenoid polyphenol and a resveratrol derivative with improved bioavailability. Polydatin possesses potential biological activities predominantly through the modulation of pivotal signaling pathways involved in inflammation, oxidative stress, and apoptosis. Various imperative biological activities have been suggested for polydatin towards promising therapeutic effects, including anticancer, cardioprotective, anti-diabetic, gastroprotective, hepatoprotective, neuroprotective, anti-microbial, as well as health-promoting roles on the renal system, the respiratory s

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… Polydatin reduces cardiotoxicity and enhances the anticancer effects of sunitinib by decreasing pro-oxidative stress, pro-inflammatory cytokines, and NLRP3 inflammasome expression Front. Oncol. 2021 11 2188 10.3389/fonc.2021.680758 34178667 PMC8226180 88. Jin Y. Zhan X. Zhang B. Chen Y. Liu C. …

The role of polyamine metabolism in remodeling immune responses and blocking therapy within the tumor immune microenvironment.

The study of metabolism provides important information for understanding the biological basis of cancer cells and the defects of cancer treatment. Disorders of polyamine metabolism is a common metabolic change in cancer. With the deepening of understanding of polyamine metabolism, including molecular functions and changes in cancer, polyamine metabolism as a new anti-cancer strategy has become the focus of attention. There are many kinds of polyamine biosynthesis inhibitors and transport inhibitors, but not many drugs have been put into clinical application. Recent evidence shows that polyamin

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… 1/2 | BENSpm in high-risk therapy | – | – PG-11047 | ODC, AMD1, SRM, SMS, SSAT, SMOX | Solid Tumors | Completed | 1 | PG-11047 in advanced refractory therapy | – | – Solid tumors and lymphoma | Completed | 1 | PG-11047 in advanced therapy | Gemcitabine, Docetaxel, Bevacizumab, Erlotinib, Cisplatin, Sunitinib …

Bone metastases in thyroid cancer.

Whereas preemptive screening for the presence of lymph node and lung metastases is standard-of-care in thyroid cancer patients, bone metastases are less well studied and are often neglected in thyroid cancer patient surveillance. Bone metastases in thyroid cancer are, however, independently associated with poor/worse prognosis with a median overall survival from detection of only 4 years despite an otherwise excellent prognosis for the vast majority of thyroid cancer patients. In this review we summarize the state of current knowledge as pertinent to bony metastatic disease in thyroid cancer,

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… Kinase inhibitor (MKI) therapy Many MKIs have been specifically investigated as therapeutics in advanced DTC and MTC, including sorafenib, lenvatinib, sunitinib, axitinib, pazopanib, motesanib, vandetanib and cabozantinib—but not specifically in the context of OMs. …

34th Annual Meeting & Pre-Conference Programs of the Society for Immunotherapy of Cancer (SITC 2019): part 1 : National Harbor, MD, USA. 6-10 November 2019.

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Prodrugs in Oncology: Bioactivation and Impact on Therapeutic Efficacy and Toxicity.

A prodrug is a molecule that lacks pharmacological activity, but upon enzymatic bioactivation, it can generate a therapeutically active molecule. The primary reason behind the design of a prodrug is to help circumvent challenges associated with the physicochemical properties of a drug molecule, such as solubility, absorption, distribution, and instability. Chemotherapy has been at the forefront of cancer treatment for over 70 years due to its ability to target rapidly proliferating tumor cells. However, a major concern with conventional chemotherapy is the lack of selectivity and its associate

An Updated Comprehensive Review on Diseases Associated with Nephrotic Syndromes.

There have been exciting advances in our knowledge of primary glomerular diseases and nephrotic syndromes in recent years. Beyond the histological pattern from renal biopsy, more precise phenotyping of the diseases and the use of modern nephrogenetics helps to improve treatment decisions and sometimes also avoid unnecessary exposure to potentially toxic immunosuppression. New biomarkers have led to easier and more accurate diagnoses and more targeted therapeutic decisions. The treatment landscape is becoming wider with a pipeline of promising new therapeutic agents with more sophisticated appr

Tumor Cell Survival Factors and Angiogenesis in Chronic Lymphocytic Leukemia: How Hot Is the Link?

Chronic lymphocytic leukemia (CLL) is characterized by the accumulation of neoplastic CD5+/CD19+ B lymphocytes in the blood. These cells migrate to and proliferate in the bone marrow and lymphoid tissues. Despite the development of new therapies for CLL, drug resistance and disease relapse still occur; novel treatment approaches are therefore still needed. Inhibition of the angiogenesis involved in the progression of CLL might be a relevant therapeutic strategy. The literature data indicate that vascular endothelial growth factor, angiopoietin-2, and matrix metalloproteinase-9 are pro-angiogen

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… Several drugs targeting angiogenesis-related pathways such as VEGF mAbs (such as bevacizumab), VEGF RTK inhibitors (such as sorafenib and sunitinib), and immunomodulatory drugs (such as thalidomide and lenalidomide) have been entered in clinical trials or are already approved for the treatment of these …

A Clinical Viewpoint on the Use of Targeted Therapy in Advanced Gastric Cancer.

The development of therapies for advanced gastric cancer (GC) has made significant progress over the past few years. The identification of new molecules and molecular targets is expanding our understanding of the disease's intricate nature. The end of the classical oncology era, which relied on well-studied chemotherapeutic agents, is giving rise to novel and unexplored challenges, which will cause a significant transformation of the current oncological knowledge in the next few years. The integration of established clinically effective regimens in additional studies will be crucial in managin

Targeting Histone Deacetylases: Opportunities for Cancer Treatment and Chemoprevention.

The dysregulation of gene expression is a critical event involved in all steps of tumorigenesis. Aberrant histone and non-histone acetylation modifications of gene expression due to the abnormal activation of histone deacetylases (HDAC) have been reported in hematologic and solid types of cancer. In this sense, the cancer-associated epigenetic alterations are promising targets for anticancer therapy and chemoprevention. HDAC inhibitors (HDACi) induce histone hyperacetylation within target proteins, altering cell cycle and proliferation, cell differentiation, and the regulation of cell death pr

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… In this sense, a clinical study has tested the safety and efficacy of vorinostat and the VEGF blocker bevacizumab in metastatic clear-cell renal cell carcinoma (ccRCC) patients that were previously undertreated with different agents, such as sunitinib, sorafenib, axitinib, and temsirolimus, among others …

Another Weapon against Cancer and Metastasis: Physical-Activity-Dependent Effects on Adiposity and Adipokines.

Physically active behavior has been associated with a reduced risk of developing certain types of cancer and improved psychological conditions for patients by reducing anxiety and depression, in turn improving the quality of life of cancer patients. On the other hand, the correlations between inactivity, sedentary behavior, and overweight and obesity with the risk of development and progression of various cancers are well studied, mainly in middle-aged and elderly subjects. In this article, we have revised the evidence on the effects of physical activity on the expression and release of the ad

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… In BC and lung cancers, the combined inhibition of apelin and angiogenesis (i.e., sunitinib) powerfully reduces tumor growth and angiogenesis rates. …

Immunologic tumor microenvironment modulators for turning cold tumors hot.

Tumors can be classified into distinct immunophenotypes based on the presence and arrangement of cytotoxic immune cells within the tumor microenvironment (TME). Hot tumors, characterized by heightened immune activity and responsiveness to immune checkpoint inhibitors (ICIs), stand in stark contrast to cold tumors, which lack immune infiltration and remain resistant to therapy. To overcome immune evasion mechanisms employed by tumor cells, novel immunologic modulators have emerged, particularly ICIs targeting cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell death protein

Metabolic reprogramming and therapeutic resistance in primary and metastatic breast cancer.

Metabolic alterations, a hallmark of cancer, enable tumor cells to adapt to their environment by modulating glucose, lipid, and amino acid metabolism, which fuels rapid growth and contributes to treatment resistance. In primary breast cancer, metabolic shifts such as the Warburg effect and enhanced lipid synthesis are closely linked to chemotherapy failure. Similarly, metastatic lesions often display distinct metabolic profiles that not only sustain tumor growth but also confer resistance to targeted therapies and immunotherapies. The review emphasizes two major aspects: the mechanisms driving

Transforming tumor microenvironments: nanotechnology and gene therapy in cellular signaling and epigenetic insight into chemo-resistance.

Chemoresistance remains the primary cause of cancer treatment failure, yet current understanding remains fragmented across isolated mechanistic studies. This review provides a unified framework linking tumor microenvironment (TME) signaling, epigenetic reprogramming, and nanotherapeutic intervention as an integrated axis driving and potentially reversing chemoresistance. We systematically examine how TME components: hypoxia (HIF-1α pathway), acidosis, cancer-associated fibroblasts (TGF-β/PDGF signaling), and immune cells (NF-κB-mediated immunosuppression) activate signaling cascades that direc

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… Imatinib (AL), Ipilimumab, Lenvatinib, Leucovorin, Lorlatinib, Losartan, Nab-paclitaxel, Neratinib (AL), Nivolumab, Olaparib, Oxaliplatin, Palbociclib, Panobinostat (AL), Pembrolizumab (AL), Pertuzumab, Ponatinib (OTHER), Quality-of-life assessments; Regorafenib, Ruxolitinib, Sirolimus, Sorafenib, Sunitinib …

Моделирование и нацеливание враждебной физико-химической ниши в метастазе костей: от экспериментальных платформ до нишевой терапии.

Метастаз рака до костей формируется не только из-за перекрестка опухолей, но и из-за враждебной физико-химической ниши, которая способствует стойкости к болезням и терапевтической недостаточности. Гипоксия, кислотность, минерализированная матричная архитектура, изменённая механика, интерстициальное давление, дисфункция перфузии и ограниченный перенос наркотиков влияют на метастатическое семя, общность, реактивацию, реконструкцию, боль и реакцию на лечение. Обычные two- размерные культуры и многие упрощенные three- размерные системы воспроизводят только отдельные особенности этой среды, часто п

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… In a microfluidic bone perivascular niche, fluid flow diminished cancer cell proliferation and decreased the efficacy of the anti-proliferative agent sunitinib relative to static settings, suggesting that flow and vessel-like barriers provide more authentic drug exposure and resistance profiles ( Crippa …

Determining Risk Factors Associated with Cardiovascular Complications in Patients with Acute Leukemia: A Systematic Review.

BackgroundPatients with acute leukemia (AL) are at heightened risk of cardiovascular complications due to both disease-related and treatment-related factors. These complications include heart failure, arrhythmias, myocardial infarction, and thromboembolic events which may significantly impact morbidity and mortality.ObjectiveTo identify the risk factors contributing to cardiovascular complications in patients with acute leukemia.MethodsThis systematic review was conducted according to the PRISMA reporting guideline. Multiple databases including PubMed, Scopus, IEEE Xplore, the Cochrane Library

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… of individualized monitoring. 35 | Berisha et al. [ 62 ]/2023 | Qualitative study (narrative review) | To examine the cardiovascular toxicity of TKIs used in treating Ph-positive leukemias and other cancers, with a particular focus on the effects of ponatinib, as well as other TKIs like sorafenib, sunitinib …

Advances in Extracellular Matrix-Associated Diagnostics and Therapeutics.

The extracellular matrix (ECM) is the common denominator of more than 50 chronic diseases. Some of these chronic pathologies lead to enhanced tissue formation and deposition, whereas others are associated with increased tissue degradation, and some exhibit a combination of both, leading to severe tissue alterations. To develop effective therapies for diseases affecting the lung, liver, kidney, skin, intestine, musculoskeletal system, heart, and solid tumors, we need to modulate the ECM's composition to restore its organization and function. Across diverse organ diseases, there are common denom

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… overall survival and progression-free survival outcomes, with specific markers showing the predictive potential for an improved outcome with monoclonal antibodies nivolumab and ipilimumab, which block programmed death-1 (PD-1) and cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4), compared with sunitinib …

"Complimenting the Complement": Mechanistic Insights and Opportunities for Therapeutics in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver and a leading cause of death in the US and worldwide. HCC remains a global health problem and is highly aggressive with unfavorable prognosis. Even with surgical interventions and newer medical treatment regimens, patients with HCC have poor survival rates. These limited therapeutic strategies and mechanistic understandings of HCC immunopathogenesis urgently warrant non-palliative treatment measures. Irrespective of the multitude etiologies, the liver microenvironment in HCC is intricately associated with chronic

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… Second-line therapies for advanced HCC that are intolerant to first-line treatment include Regorafenib, Cabozantinib, Sunitinib, Linifanib, Brivanib, Tivantinib, Donafenib, etc. which target tyrosine kinases, HGF-MET axis, and related pathways ( 108 ). …

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

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… . | Sorafenib, sunitinib, pazopanib, axitinib, lenvatinib, vandetanib, regorafenib, cabozantinib, anlotinib, apatinib, fruquintinib PDGFR/ KIT | Receptor tyrosine kinases that regulate proliferation, differentiation, and survival of mesenchymal and hematopoietic cells; their aberrant activation (mutations … or rearrangements) promotes tumor growth and angiogenesis. | Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia, GIST (including KIT- and PDGFRA-mutant, unresectable or metastatic disease across different lines of therapy), and other hematologic malignancies. | Imatinib, sunitinib, regorafenib …

Program-Abstracts

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… Transition 11:18 Silke Haubeiss , Stuttgart, Germany Targeting Cancer-Associated Fibroblasts (CAFs) with Small Molecule Inhibitors to Enhance Sensitivity of Tumors to Conventional Chemotherapy 11:30 Lucy Allen , Amersham, Buckinghamshire, UK Monitoring Tumour Response to the Anti-angiogenic Therapy Sunitinib …