Therapeutic Response Research Articles

An in silico approach uncovering the competency of oncolytic human adenovirus 52 for targeted breast cancer virotherapy

Breast cancer remains a major health threat throughout the world specifically in women above 30 years of age however, it is rarely known to affect men as well. It is characterized by the abnormal division of cells in the breast tissue resulting in the development of breast malignancies. Various risk factors contributing to breast cancer include age, family history, genetic mutations (chiefly in BRCA1 and BRCA2 genes) along with hormonal imbalances (oestrogen, progesterone, HER2). Early detection which can be obtained through frequent rounds of self-examination, mammographic scanning, and clinical assessment plays a crucial role in the prevention of the disease. In addition, appropriate diagnosis assists in better therapeutic responses. This study highlights the considerable health risks associated with the conventional treatment procedures which arise and increased demand of advanced, secure, and risk-free treatment alternatives. Oncolytic viruses are potentially apparent for the aim of improving cancer therapeutics with reduced side effects. These viruses act as the fundamental therapeutic agent themselves that selectively target and kill malignant cells without harm to healthy tissues. The key objective of the research is to provide evidence that Human Adenovirus 52 is a potent oncolytic virus and to highlight its capacity to target and eliminate cancer cells with precision while causing the least amount of harm to healthy tissues. Validating the in-silico method entails evaluating the precision and dependability of the computational modelling by contrasting the in-silico predictions with the findings from the experiments rank as the secondary objective. The workflow of this research utilized in-silico computational drug designing approaches including retrieval of tertiary structures of both the target Breast Cancer Type 1 Susceptibility Protein (BRCA1) and the viral Human Adenovirus 52 protein, their validation generating Ramachandran Plots determining favoured amino acid residue angles and prediction of their active residues. Furthermore, the study focused on the molecular dynamics docking of proteins, interpretation of molecular interactions between the docked complex, as well as the assessment of the molecular dynamic simulations (MD) in addition to their MMGBSA binding energy calculations. A successful docking between BRCA1 and Adenovirus protein provided a significant score of 329.2 +/- 24.3, furthermore, MD simulations showed a high RMSD peak at 2.8 Å, RMSF were maximum at 3.5 Å with highest protein–protein interaction, the radius of gyration was stable throughout the simulation representing elastic stability along with a high energy interaction value of - 7882 kCal/mol. Moreover, the MMGBSA calculation results showed a notable release of binding free energy of - 68.96 kCal/mol demonstrating effective bond formation between the docked complex. These findings propose the effectiveness of Human Adenovirus 52 to treat cancer. The selected oncolytic Human Adenovirus 52 is a potential candidate for the target specific treatment of breast cancer through virotherapy. This computer-aided drug discovery presents significant potential in targeting cancer cells and would assist in the development of potent drug reagents for the cancer therapy.

3D-printed brachytherapy in patients with cervical cancer: improving efficacy and safety outcomes

ObjectiveThis study aims to evaluate the efficacy and safety of 3D printing technology in brachytherapy for cervical cancer, comparing its outcomes with conventional free hand implantation brachytherapy.MethodsA total of 50 cervical cancer patients treated at the First Affiliated Hospital of Gannan Medical College from January 2019 to July 2023 were included in this study. Patients were divided into two groups: 25 patients received intensity-modulated radiotherapy (IMRT) combined with 3D-printed brachytherapy, and 25 patients underwent IMRT combined with free hand brachytherapy implantation. Key indicators analyzed included short-term therapeutic effects, survival outcomes, operation times, the number of CT scans, the number of needles inserted, dosimetric parameters, and complications.ResultsThe use of 3D-printed brachytherapy significantly improved the safety of radiation therapy operations, especially for large tumors (≥ 30 mm), by providing more precise dose distribution and reducing the radiation doses received by critical organs such as the bladder and rectum. Compared to the artificial implant group (88% prevalence), the 3D-printed brachytherapy group showed a significantly lower incidence of radiation enteritis (29.2% prevalence, p < 0.001). There were no significant differences in other complications between the two groups. For instance, the incidence of radiation cystitis was relatively high in the 3D-printed brachytherapy group (79.2% prevalence) compared to the artificial implant group (64% prevalence, p = 0.240). The median follow-up period in this study was 22.5 months [IQR 18–29]. Among the 49 patients included, 43 had cervical squamous carcinoma and 6 had cervical adenocarcinoma. Short-term therapeutic response rates were comparable, with no significant difference in overall survival observed between the two groups.Conclusion3D-printed brachytherapy offers a more effective and safer therapeutic option for patients with cervical cancer, particularly for those with large tumors or complex anatomical structures.

Efficacy and safety of topical spironolactone versus topical dapsone in the treatment of acne vulgaris.

Acne vulgaris is a common skin disease that greatly impacts the quality of life of affected individuals. Several treatment modalities are available for acne, with variable degrees of success. Our aim was to compare the safety and efficacy of topical spironolactone 5% gel and topical dapsone 5% gel as treatment modalities for acne vulgaris. The study included 28 patients with mild to moderate acne. They were randomly divided into two equal groups. Group I treated with topical spironolactone 5% gel, and group II treated with topical dapsone 5% gel. In both groups, the gel was applied twice daily for 12 weeks, and patients were evaluated using the acne severity index. Group I included 14 patients [11 (78.6%) females and 3 (21.4%) males]. More than one-half of this group (64.3%) had moderate acne severity. Group II included 14 patients [12 (85.7%) females and 2 (14.3%) males]. Half of patients had moderate acne severity. Therapeutic response was poor, moderate, good, and excellent (14.3%), (28.6%), (50%), (7.1%), respectively, in topical spironolactone group versus poor, moderate, and good (50%), (42.9%), (7.1%), respectively, in topical dapsone group. The therapeutic response between the studied groups was statistically significant in favor of the topical spironolactone group. Regarding adverse effects, burning sensation was evident after application of topical spironolactone while itching was significantly common with topical dapsone. The data provided by the current study support the use of topical spironolactone 5% gel in treating acne vulgaris in both male and female patients.

Review article: Optimisation of biologic (monoclonal antibody) therapeutic response in inflammatory bowel disease.

There are a plethora of therapeutic options for the management of inflammatory bowel disease (IBD). Despite this, clinical outcomes with standard dosing often fall short of established targets. While efforts centre on developing novel therapies, there is an ongoing need to optimise the use of existing agents. To focus on strategies to optimise response to biologic (monoclonal antibody) therapies in IBD, including use of therapeutic drug monitoring (TDM). An extensive review of the published literature. TDM is a strategy aimed at enhancing the effectiveness of drugs with variable exposure-response relationships by measuring serum concentrations of biologic therapies and detecting neutralising antibodies. Reactive TDM is performed when therapeutic goals have not been achieved. Tumour necrosis factor alpha (TNF) inhibitors are the treatment class most frequently associated with immunogenicity and loss of response. Immunogenicity can be reduced through avoidance of low serum drug concentrations by dose optimisation or use of concomitant immunomodulator therapy. Subtherapeutic dosing in the absence of antidrug antibodies is best managed by dose escalation or dose interval reduction. Persistent neutralising drug antibodies necessitate switching to an alternative therapy. Proactively ensuring adequate serum trough levels might help sustain treatment durability and prevent loss of response. Newer non-TNF inhibitors demonstrate less robust exposure-response relationships, and TDM may not prove as beneficial. In the treat-to-target paradigm of IBD treatment, optimising treatment effect with dose optimisation, which may involve strategies including TDM, increases the likelihood of achieving clinical remission and may accomplish deeper levels of remission beyond symptom control.

Prenatal Supplementation of Docosahexaenoic Acid for the Management of Preterm Births: Clinical Information for Practice.

Unhealthy pregnancy and the resultant abnormalities in newborns exhibit a significant drawback. Each year, an estimated 15 million babies are born prematurely, accounting for the majority of deaths among children under the age of 5. India accounts for about a quarter of all preterm birth (PTB) incidences, with few therapeutic options available. However, research shows that consuming more marine foods (rich in omega-3 fatty acids (Ω-3), particularly Docosahexaenoic acid (DHA), helps to maintain a healthy pregnancy and can manage or prevent the onset of PTB and its accompanying difficulties. Present circumstances raise concerns about the use of DHA as a medication due to a lack of evidence on the dosage requirements, safety profile, molecular route, and commercially accessible strength for their therapeutic response. Several clinical experiments have been done over the last decade; however, the mixed outcomes have resulted in discrepancies. Most scientific organizations suggest a daily DHA consumption of 250-300 mg. However, this may differ from person to person. As a result, before prescribing a dosage, one should check the DHA concentrations in the individual's blood and then propose a dose that will benefit both the mother and the unborn. Thus, the review focuses on the favourable benefits of Ω-3, particularly DHA during pregnancy and postpartum, therapeutic dose recommendations, safety considerations, particularly during pregnancy, and the mechanistic pathway that might prevent or reduce the frequency of PTB accidents.

The impact of Charcot-Leyden Crystal protein on mesothelioma chemotherapy: targeting eosinophils for enhanced chemosensitivity

In mesothelioma (MPM), clinical evidence indicates that the absolute eosinophil count negatively correlates with overall survival and response to standard chemotherapy. Since eosinophils poorly infiltrate MPM tumours, we hypothesised that endocrine rather than paracrine pathways mediate the therapeutic response. We thus studied the effect of eosinophil-associated factors on response to chemotherapy in mesothelioma. The culture supernatant conditioned by primary human eosinophils was added to mesothelioma cells in presence of the standard chemotherapeutic regimen. The effectiveness of an anti-eosinophil treatment was evaluated in a preclinical model of C57BL/6 mice transplanted with mesothelioma tumour cells. Supernatant of eosinophils differentiated from EOL1 cells or directly isolated from peripheral blood inhibited apoptosis induced by cisplatin and pemetrexed in 2D cultures and in spheroids. Transcriptomic analysis indicated that the anti-apoptotic effect mediated by eosinophils involved molecular interactions with the Charcot-Leyden Crystal protein or Galectin-10 (CLC-P/Gal10). The functional relevance of CLC-P/Gal10 was demonstrated by antibody-mediated depletion. Recombinant human CLC-P/Gal10 mimicked the anti-apoptotic activity of eosinophil-derived supernatants. In the mouse model, eosinophilia did not significantly affect tumour growth but altered the response to chemotherapy. Finally, pretreatment of eosinophilia with the anti-Siglec-F antibody before chemotherapy restored the effectiveness of the treatment. This study provides a mechanistic rationale to clinical evidence correlating the poor outcome of patients with mesothelioma and with eosinophil-derived CLC-P/Gal10, opening new prospects for intervention in this fatal solid tumour. Belgian Foundation against Cancer, Fonds National de la Recherche Scientifique (FNRS), Télévie, Foundation Léon Fredericq, ULiège.

Subcellular expression of CD30 in cutaneous mastocytosis-An important factor for targeted treatment.

The subcellular distribution of CD30 on mast cells and the presence of eosinophils in cutaneous mastocytosis require further investigation, especially as the cell surface expression of CD30 is critical for the therapeutic response of systemic mastocytosis to brentuximab vedotin. Investigation of 147 biopsy specimens from 143 patients with cutaneous mastocytosis for mast cell density and distribution, frequency of CD30 expression, CD30 staining patterns, and presence and distribution of eosinophils. Correlation with clinical patterns. Retrospective multicenter immunohistochemical study of CD30 expression, eosinophils and basic clinical data in cutaneous mastocytosis. CD30 expression was found in all samples (cut-off: ≥1%), whereby the staining was predominantly cytoplasmic in 99% of the samples. Additional membrane staining was detected in 62% of the samples. Surface expression of CD30 was more common in biopsy specimens with a high mast cell burden and in biopsy specimens with a higher CD30 expression rate. Eosinophils were admixed in 58% of the samples. Females and older patients showed a trend of a lower mast cell burden. Retrospective study on formalin-fixed and paraffin-embedded tissue without functional analysis. Most cases of cutaneous mastocytosis show cell surface expression of CD30 expression and is, therefore, in principle, accessible for therapy with antibodies against CD30, provided the overall situation of the patient warrants.

Deciphering the role of NcRNAs in Pancreatic Cancer immune evasion and drug resistance: a new perspective for targeted therapy

Pancreatic cancer (PC) is a very aggressive digestive system tumor, known for its high mortality rate, low cure rate, low survival rate and poor prognosis. In particular, pancreatic ductal adenocarcinoma (PADC), which accounts for more than 90% of PC cases, has an overall 5-year survival rate of only 5%, which is an extremely critical situation. Early detection and effective treatment of PC is extremely difficult, which leads many patients to despair. In the current medical context, targeted therapy, as an important strategy for cancer treatment, is expected. However, the problems of immune escape and drug resistance in PC have become two major obstacles that are difficult to be overcome by targeted therapy. How to break through these two difficulties has become a key issue to be solved in the field of PC therapy. In recent years, non-coding RNAs (ncRNAs) have continued to heat up in the field of cancer research. NcRNAs play a pivotal role in gene regulation, cell differentiation, development, and disease processes, and their important roles in the genesis, development, and therapeutic response of PC have been gradually revealed. More importantly, ncRNAs have many advantages as therapeutic targets, such as high specificity and low side effects, making them a new favorite in the field of PC therapy. Therefore, the aim of this paper is to provide new ideas and methods for the targeted therapy of PC by reviewing the mechanism of action of four major ncRNAs (circRNAs, lncRNAs, miRNAs, siRNAs) in both immune escape and drug resistance of PC. It is expected that an effective way to overcome immune escape and drug resistance can be found through in-depth study of ncRNA, bringing a ray of hope to PC patients.

Fractional CO2 Laser-Assisted Delivery of Botulinum Toxin-A Versus Aluminum Chloride in Treatment of Primary Palmar Hyperhidrosis.

Primary palmar hyperhidrosis (PPH) constitutes a distressing dermatologic condition that greatly affects patients' quality of life. Its management still needs to be addressed to find a suitable therapeutic modality that is readily available, cost effective, and gives patients a quite long disease-free period. To assess the efficacy of fractional CO2 laser as a delivery method for botulinum toxin-A (BTX-A) and aluminum chloride in treating PPH. Twenty-four subjects with PPH were treated on both hands with fractional CO2 laser followed on the right hand with topical BTX-A and on the left hand with topical aluminum chloride. Minor's starch-iodine test and Hyperhidrosis Disease Severity Scale (HDSS) were used for evaluation of treatment response and for follow-up. There was a significant improvement in HDSS in both groups, but there was no statistically significant difference in the therapeutic response for both modalities. There was a statistically significant longer disease-free period in the BTX-A-treated hands. Fractional CO2 laser-assisted drug delivery (LADD) represents a safe, minimally invasive procedure that enhances the delivery of BTX-A and aluminum chloride, the two most widely used agents for treating PPH, with a comparable anhidrotic response.

Unravelling the Reasons Behind Limited Response to Anti-PD Therapy in ATC: A Comprehensive Evaluation of Tumor-Infiltrating Immune Cells and Checkpoints.

Inhibiting the immune checkpoint (ICP) PD-1 based on PD-L1 expression status has revolutionized the treatment of various cancers, yet its efficacy in anaplastic thyroid carcinoma (ATC) remains limited. The therapeutic response depends upon multiple factors, particularly the conduciveness of the tumor's immune milieu. This study comprehensively evaluated and classified ATC's immune microenvironment (IME) to elucidate the factors behind suboptimal response to anti-PD therapy. Utilizing multiplex-immunofluorescence and immunohistochemistry, we retrospectively analyzed 26 cases of ATC for expression of ICPs PD-L1, PD-1, CTLA4, TIM3, and Galectin-9 and tumor-infiltrating cytotoxic T lymphocytes (CTL)-the effector cells, the anti-tumor NK cells, the immune-inhibitory myeloid-derived suppressor (MDSC) and regulatory T (Treg) cells, and B lymphocytes. Most ATCs (65%) exhibited PD-L1 positivity, but only 31%, in addition, had abundant CTL (type I IME), a combination associated with a better response to ICP inhibition. Additionally, PD-1 expression levels on CTL were low/absent in most cases-a "target-missing" situation-unfavorable for an adequate therapeutic response. All but one ATC showed nuclear Galectin-9 expression. The documentation of nuclear expression of Galectin-9 akin to benign thyroid is a first, and its role in ATC pathobiology needs further elucidation. In addition to less abundant PD-1 expression on CTL, the presence of MDSC, Treg, and exhausted cytotoxic T lymphocytes in the immune milieu of ATC can contribute to anti-PD resistance. TIM3, the most frequently expressed ICP on CTL, followed by CTLA4, provides alternate therapeutic targets in ATC. The co-expression of multiple immune checkpoints is of great interest for ATC since these data also open the avenue for combination therapies.

Oxidative Stress and Antioxidants in Pediatric Asthma’s Evolution and Management

Within the pediatric population, bronchial asthma is one of the most prevalent chronic respiratory system diseases. The number of exacerbations, severity, and duration of symptoms all have a significant impact on children’s life quality. In the last decades, the prevention and management strategies of this pathology have focused on maintaining or even increasing the pulmonary function to maximum levels in early childhood, as it has been demonstrated that functional deficits at this level occurring before school age cause pathological manifestations later, in adulthood. The epithelium of the airways and implicitly that of the lung is the first barrier against the lesions caused by pro-oxidative factors. Both oxidative and antioxidative factors can be of endogenous origin (produced by the body) or exogenous (from the environment or diet). Good functioning of antioxidant defense mechanisms from the molecular level to the tissue level, and a balance between pro-oxidative factors and anti- oxidative factors, influence the occurrence of compensatory mechanisms at the level of the respiratory epithelium, causing the delay of local responses to the stress induced by chronic inflammation (bronchial remodeling, thickening of airway smooth muscles, bronchoconstriction, bronchial hyper-reactivity). These mechanisms underlie the pathophysiological changes in asthma. Numerous studies carried out among the pediatric population inclusively have demonstrated the effectiveness of antioxidants in the prophylaxis, slowing down and preventing the progression of this pathology. This review complements the scientific articles, aiming at emphasizing the complexity of oxidative physio-pathological pathways and their importance in the occurrence, development, and therapeutic response in asthma, providing a good understanding of the relationship between oxidative and antioxidative factors, and being a source of future therapeutic strategies.

Microbiological aspects of cancer progression: A systematic review conducted according to the PRISMA 2020 guidelines and the Cochrane Handbook for Systematic Reviews of Interventions.

The complex interplay between the gut microbiota, cancer treatments and patient characteristics has emerged as a significant area of research. This study sought to examine these relationships in the context of colorectal cancer (CRC).A comprehensive search of relevant studies was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines and the Cochrane Handbook for Systematic Reviews of Interventions. The studies included a variety of treatment modalities and microbiological parameters. A data extraction form, designed specifically for this review, was used to assess a range of variables across all studies.The analysis revealed a multifaceted interaction between the gut microbiota, genetic factors and treatment outcomes. Elderly patients with CRC frequently received single-agent chemotherapy, with outcomes that were comparable to those of younger patients. The presence of tumorigenic bacteria, including Escherichia coli and Bacteroides fragilis, was associated with early colon neoplasia. Additionally, an abundance of Fusobacterium spp. was observed in colonic adenomas, contributing to a pro-inflammatory environment. Although the FcγRIIIa-158 V/V genotype was associated with higher cetuximab-mediated antibodydependent cellular cytotoxicity (ADCC), no direct influence of FcγR polymorphisms on treatment response was noted. Furthermore, the combination of programmed cell death protein-1 (PD-1), BRAF and MEK inhibition showed favorable response rates. The gut microbiome, especially the presence of Fusobacterium spp., had a notable influence on the therapeutic response in CRC.These findings underscore the role of the gut microbiota and genetic factors in cancer treatment outcomes, emphasizing the potential of a holistic approach to cancer management. Future research should exploit these findings in order to develop microbiota-modulating strategies and personalized medicine approaches for the purpose of improving the efficacy of cancer treatment.

E2F1-induced autocrine IL-6 inflammatory loop mediates cancer-immune crosstalk that predicts T cell phenotype switching and therapeutic responsiveness

Melanoma is a metastatic, drug-refractory cancer with the ability to evade immunosurveillance. Cancer immune evasion involves interaction between tumor intrinsic properties and the microenvironment. The transcription factor E2F1 is a key driver of tumor evolution and metastasis. To explore E2F1’s role in immune regulation in presence of aggressive melanoma cells, we established a coculture system and utilized transcriptome and cytokine arrays combined with bioinformatics and structural modeling. We identified an E2F1-dependent gene regulatory network with IL6 as a central hub. E2F1-induced IL-6 secretion unleashes an autocrine inflammatory feedback loop driving invasiveness and epithelial-to-mesenchymal transition. IL-6-activated STAT3 physically interacts with E2F1 and cooperatively enhances IL-6 expression by binding to an E2F1-STAT3-responsive promoter element. The E2F1-STAT3/IL-6 axis strongly modulates the immune niche and generates a crosstalk with CD4+ cells resulting in transcriptional changes of immunoregulatory genes in melanoma and immune cells that is indicative of an inflammatory and immunosuppressive environment. Clinical data from TCGA demonstrated that elevated E2F1, STAT3, and IL-6 correlate with infiltration of Th2, while simultaneously blocking Th1 in primary and metastatic melanomas. Strikingly, E2F1 depletion reduces the secretion of typical type-2 cytokines thereby launching a Th2-to-Th1 phenotype shift towards an antitumor immune response. The impact of activated E2F1-STAT3/IL-6 axis on melanoma-immune cell communication and its prognostic/therapeutic value was validated by mathematical modeling. This study addresses important molecular aspects of the tumor-associated microenvironment in modulating immune responses, and will contribute significantly to the improvement of future cancer therapies.

HLA-DRB1*01 predicts treatment outcome in juvenile idiopathic arthritis: A retrospective-prospective cohort study.

Juvenile idiopathic arthritis (JIA) is the most common chronic inflammatory autoimmune disease in childhood, significantly contributing to both short- and long-term disability. While certain human leukocyte antigen (HLA) class II alleles are known to be associated with specific subgroups of JIA, emerging evidence suggests a strong correlation between these alleles and treatment response. This study involved 143 JIA patients diagnosed according to International League of Associations for Rheumatology criteria. Each patient underwent HLA class II typing, including HLA-B27, as well as tests for rheumatoid factor (RF) and antinuclear antibodies (ANA). Comprehensive rheumatological assessments were conducted at diagnosis, with follow-ups at three and six months post-onset. After six months of methotrexate (MTX) treatment, patients were categorized as responders or non-responders. Responders achieved clinically inactive disease based on the American College of Rheumatology Provisional Criteria for Defining Clinical Inactive Disease and Clinical Remission. Non-responders, who did not reach clinically inactive disease after six months of treatment, required the addition of another non-biological disease-modifying antirheumatic drug (DMARD) or a biological DMARD. Our analysis revealed that the HLA-DRB1*01 allele is a significant prognostic marker for therapeutic response, predicting therapeutic resistance (P=0.01). The most prevalent HLA-DRB1 alleles in the treatment-resistant group were HLA-DRB1*08:11 (11.3%), HLA-DRB1*01:01 (8.5%), HLA-DRB1*01:13, HLA-DRB1*04:11 (7%), HLA-DRB1*08:13, and HLA-DRB1*08:15 (4.2%). These findings highlight the critical role of HLA class II alleles in pediatric rheumatology, particularly in relation to treatment response and disease prognosis. In the era of personalized medicine, understanding the genetic contributions to treatment response and outcomes in JIA patients is essential. A key limitation of this study was the lack of comparison of treatment responses across different JIA subtypes. Future studies should prioritize evaluating MTX efficacy within specific JIA subgroups to enable a more tailored understanding of its effectiveness.

The signature of SARS-CoV-2-related genes predicts the immune therapeutic response and prognosis in breast cancer

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an exceptionally contagious single-stranded RNA virus with a strong positive contagion. The COVID-19 pandemic refers to the swift worldwide dissemination of SARS-CoV-2 infection, which began in late 2019. The COVID-19 epidemic has disrupted many cancer treatments. A few reports indicate that the prevalence of SARS-CoV-2 has disrupted the treatment of breast cancer patients (BCs). However, the role of SARS-CoV-2 in the occurrence and prognosis of BC has not been elucidated. Here, we applied bioinformatics to construct a prognostic signature of SARS-CoV-2-related genes (SCRGs). Specifically, weighted gene co-expression network analysis (WGCNA) was utilized to extract co-expressed genes of differentially expressed genes (DEGs) in breast cancer and SCRGs. Then, we utilized the least absolute shrinkage and selection operator (LASSO) algorithm and univariate regression analysis to screen out three hub genes (DCTPP1, CLIP4 and ANO6) and constructed a risk score model. We further analyzed tumor immune invasion, HLA-related genes, immune checkpoint inhibitors (ICIs), and sensitivity to anticancer drugs in different SARS-CoV-2 related risk subgroups. In addition, we have developed a nomination map to expand clinical applicability. The results of our study indicate that BCs with a high-risk score are linked to negative outcomes, lower immune scores, and reduced responsiveness to anticancer medications. This suggests that the SARS-CoV-2 related signature could be used to guide prognosis assessment and treatment decisions for BCs.

Endoscopic morphology of gastric MALT lymphoma correlate with API2/MALT1 fusion and predict treatment response after helicobacter pylori eradication

BackgroundThe presence of API2/MALT1 fusion in gastric mucosa-associated lymphoid tissue (MALT) lymphoma predicts poor response to Helicobacter pylori (Hp) eradication therapy. This study aimed to assess the correlation between endoscopic morphology of MALT lymphoma and API2/MALT1 fusion and evaluate treatment response to Hp eradication based on morphological subtypes.MethodsA retrospective review was conducted on patients diagnosed with gastric MALT lymphoma between January 2011 and December 2022. Endoscopic morphology was categorized as superficial, non-superficial, or mixed type. The superficial type was further classified into gastritis superficial lesion and localized superficial lesion based on border clarity. Logistic regression models evaluated the impact of clinical and endoscopic characteristics on anti-Hp therapy effectiveness.ResultsAmong the 114 patients included, 93 (81.6%) were Hp-positive, and API2/MALT1 fusion was detected in 58 (50.9%) cases, The superficial type was the predominate morphology (73/114, 64%). The regular arrangement of collecting venules (RAC) sign was noted in 21 (18.4%) cases. In superficial subtypes, the RAC signs were more frequently observed in localized lesion than gastritis lesion (35.6% vs. 7.1%, p = 0.01). and the superficial localized lesion was more common in individuals with positive API/MALT1 fusion than negative ones (76.9% vs. 44.1%, p = 0.01). Following Hp eradication, the remission rate for localized lesion was 34.3%, significantly lower than for gastritis lesion (66.7%, p = 0.01). Both endoscopic morphology (OR = 0.26, 95% CI 0.09–0.75) and API2-MALT1 fusion (OR = 14.29, 95% CI 4.19–48.67) impacted the efficacy of anti-Hp therapy. However, multivariate analysis identified API2-MALT1 fusion as the only independent predictor of treatment outcome (OR = 12.18, 95% CI 3.49–42.55, p < 0.001).ConclusionGastric MALT lymphomas with superficial-type morphology, particularly those with defined borders resembling early gastric cancer, were associated with API2/MALT1 fusion and a lower remission rate after Hp eradication therapy. This suggests that endoscopic morphology, along with API2/MALT1 fusion status, could help predict the therapeutic response, with API2/MALT1 fusion serving as a critical indicator of treatment resistance.

A guideline on biomarkers in the diagnosis and evaluation in axial spondyloarthritis

ObjectiveTo develop a guideline for selecting biomarkers in the diagnosis and assessment in patients with axial spondyloarthritis (axSpA).MethodA joint effort was carried out by the core team, the literature review team and the multidisciplinary voting panel to formulate recommendations regarding biomarkers in axSpA, using an evidence-based and consensus-based strategy. Certainty of evidence and strength of recommendation were determined, and levels of agreement within the voting panel were calculated.ResultsA total of 20 recommendations were formulated in this guideline, with levels of agreement ranging from 6.48 to 9.71. The two strong recommendations, HLA-B27 testing in patients suspected of axSpA and regular-interval monitoring of CRP/ESR represent the status quo of axSpA evaluation, while the 13 conditional recommendations represent the promising biomarkers with clinical utility in diagnosis, disease activity assessment, prediction of radiographic progression and therapeutic responses. This guideline does not dictate clinical choices of tests on axSpA, and decisions should be made based on comprehensive consideration of costs, accessibility, patients’ values and willingness as well as the objective of testing in the local context.ConclusionThis guideline addresses the interpretation of the clinical significance of biomarkers in axSpA, and the biomarkers endorsed in this guideline composed a clinical toolkit for healthcare professionals to choose from.

Multi-Target Peptide Nanofiber Immunotherapy Diminishes Complement Anaphylatoxin Activity in Acute Inflammation.

The anaphylatoxins C3a and C5a are products of the complement cascade that play important and interrelated roles in health and disease. Both are potential targets for anti-inflammatory active immunotherapies in which a patient's own immune system is stimulated to produce therapeutic immune responses against problematic self-molecules. However, the complex and time-dependent interrelations between the two molecules make dual targeting challenging. To investigate a dual-target active immunotherapy against C3a and C5a and to systematically study the effect of varied degrees of responses against both targets, the study employed self-assembled peptide immunogens capable of displaying a broad range of epitope compositions and Design-of-Experiments (DoE) approaches. Peptide nanofibers contained B-cell epitopes of C3a and C5a in defined quantities, and intranasal immunization raised systemic and mucosal immunity against each target. In a lipopolysaccharide-induced model of sepsis, increasing anti-C5a responses are protective, whereas increasing anti-C3a responses are detrimental, and survival rates are negatively correlated with anti-C3a/anti-C5a IgG titer ratio. This work highlights the interplay between the two molecules by making use of a modular, defined, and easily adjusted biomaterial-based active immunotherapy platform.

Disseminated Superficial Actinic Porokeratosis Treated with Topical Simvastatin: Evaluation of Therapeutic Response with Dermoscopy

Disseminated Superficial Actinic Porokeratosis Treated with Topical Simvastatin: Evaluation of Therapeutic Response with Dermoscopy

Status of and Challenges in Therapy of Mucinous Ovarian Cancer Associated with Pseudomyxoma Peritonei Syndrome: Review of Current Options and Future Treatment Trends

Objective: Pseudomyxoma peritonei (PP) is a rare condition, and differentiating between primary and secondary ovarian causes is crucial for determining the appropriate oncological therapy. Given the resistance of ovarian mucinous carcinoma to standard platinum-based chemotherapy, the objective of this review is to present the current therapeutic approaches and summarize the emerging trends in the treatment of this disease. Methods: The authors conducted an exhaustive evaluation of studies published over a 14-year period (June 2010–May 2024) concerning pseudomyxoma peritonei, mucinous ovarian carcinoma, ovarian causes of PP, and ovarian cancer using the following databases: PubMed, Scopus, and Science Direct. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. The results were organized into seven subchapters and analyzed. Results: The analyzed studies present surgery followed by HIPEC as the current therapy with the best long-term survival results. However, the oncological treatment is unsatisfactory, and the choice of therapy depending on the primary origin of the tumor becomes particularly important. For the differential diagnosis between pseudomyxoma due to a gastrointestinal cause and that of ovarian origin, genetic analyses are recommended; these include the characteristics of the mucin present in the lesion, as the therapeutic response can have contradictory results depending on the primary origin of the tumor. Conclusions: Surgery followed by HIPEC remains the standard for resectable cases. However, oncological treatment has controversial results in the case of mucinous ovarian carcinoma compared to other types of ovarian cancer and to metastatic ovarian tumors associated with pseudomyxoma of the peritoneum. Based on the articles included in this review, it was found that the current trend is the study of mucin as a resistance factor against chemotherapy based on platinum products and the targeting of oncological therapy according to the tumor’s genetic characteristics.