Efficacy Of Treatment Research Articles

Promising Therapeutic Strategies for Hematologic Malignancies: Innovations and Potential.

In this review we explore innovative approaches in the treatment of hematologic cancers by combining various therapeutic modalities. We discuss the synergistic potential of combining inhibitors targeting different cellular pathways with immunotherapies, molecular therapies, and hormonal therapies. Examples include combining PI3K inhibitors with proteasome inhibitors, NF-κB inhibitors with immunotherapy checkpoint inhibitors, and neddylation inhibitors with therapies targeting the tumor microenvironment. Additionally, we discuss the potential use of small molecules and peptide inhibitors in hematologic cancer treatment. These multidimensional therapeutic combinations present promising strategies for enhancing treatment efficacy and overcoming resistance mechanisms. However, further clinical research is required to validate their effectiveness and safety profiles in hematologic cancer patients.

Significance of novel PANoptosis genes to predict prognosis and therapy effect in the lung adenocarcinoma

Lung adenocarcinoma (LUAD) is the dominant histotype of non-small cell lung cancer. Panoptosis, a comprehensive form of programmed cell death, is central to carcinogenesis. In this study, the expression of PANoptosis-related genes (PRGs) and their impact on the development, prognosis, tumor microenvironment, and treatment response of patients with lung adenocarcinoma (LUAD) were systematically evaluated. PRGs were selected from The Cancer Genome Atlas database and Genecards dataset using differential expression analysis. The signature of included PRGs was identified using univariate Cox regression analysis and LASSO regression analysis. Additionally, a nomogram was developed that includes signature and clinical information. Kaplan–Meier survival analysis and receiver operating characteristic curves were used to assess the predictive validity of these risk models. Finally, functional analysis of the selected PRGs in signature and analysis of immune landscape were also performed. Preliminary identification of 10 genes related to PANoptosis has significant implications for prognosis. Subsequently, seven related genes were integrated to classify LUAD patients into different survival risk groups. The prognostic risk score generated from the signature and the TNM stage were as independent prognostic factors and were utilized in creating a nomogram plot. Both the features and the nomogram plot showed accurate performance in predicting the overall survival of LUAD patients. The PRGs were enriched in several biological functions and pathways, and stratified studies were conducted on the differences in immune landscape between high-risk and low-risk groups based on their characteristics. Ultimately, our evaluation focused on the differences in drug treatment efficacy between the high-risk and low-risk groups, providing a foundation for future research directions. Potential associations between PRGs and patient prognosis in LUAD have been identified in this study. Potential biomarkers for clinical application could be considered for the prognostic predictors identified in this study.

Cost per treatment responder analysis of atogepant compared to rimegepant for the preventive treatment of episodic migraine.

To estimate the number needed to treat and cost per additional responder for atogepant and rimegepant versus placebo for the preventive treatment of episodic migraine (EM) in the United States. Migraine has an enormous impact on a person's daily activities and quality of life, and results in significant clinical and economic burden to both individuals and society. It is important to understand the comparative efficacy and economic value of oral calcitonin gene-related peptide receptor antagonists (gepants) for preventive treatment of EM. Currently, atogepant and rimegepant are US Food and Drug Administration approved for preventive treatment of migraine (rimegepant for EM and atogepant for EM and for chronic migraine). In the absence of head-to-head trials, we utilized an indirect treatment comparison on efficacy data from clinical trials conducted for the preventive treatment of EM. We estimated number needed to treat, a valuable metric used in clinical practice to compare treatment efficacy, and cost per additional responder, which can be used to establish the cost effectiveness of a treatment. An indirect treatment comparison was conducted to compare the efficacy of atogepant 60 mg once daily and rimegepant 75 mg once every other day as preventive treatments for EM using published data from the registrational trials of atogepant (ADVANCE) and rimegepant (BHV3000-305). The efficacy outcome of interest was ≥50% reduction from baseline in mean monthly migraine/headache days (≥50% responder rate), which was variably defined for a base case and two scenario analyses. Number needed to treat and cost per additional responder versus placebo were calculated and compared between both treatments (weeks 9-12 in the base case analysis; weeks 1-12 and 9-12 for atogepant and during weeks 9-12 for rimegepant in the scenario analyses). In the base case analysis, ≥50% responder rates were 64.9% (95% confidence interval [CI], 53.9-74.5) for atogepant and 51.8% (95% CI, 42.9-60.6) for rimegepant, compared to 44.1% (95% CI, 39.4-49.0) for placebo. The median number needed to treat versus placebo in the base case scenario was 4.8 (95% CI, 3.1-9.0) for atogepant compared to 13.0 (95% CI, 5.9-75.1) for rimegepant. The cost per additional responder versus placebo in the base case scenario was estimated to be $15,823 (95% CI, $11,079-$29,516) for atogepant compared to $73,029 (95% CI, $32,901-$422,104) for rimegepant. Results of the two scenario analyses were consistent with the base case analysis. Atogepant had substantially lower numbers needed to treat and costs per additional responder versus placebo than rimegepant for the preventive treatment of EM across all evaluated scenarios. These analyses suggest that atogepant may be more cost effective than rimegepant for the preventive treatment of EM. Limitations include differences in inclusion/exclusion criteria and in reporting of the ≥50% responder rates between trials.

Neuroimaging markers of aberrant brain activity and treatment response in schizophrenia patients based on brain complexity

The complexity of brain activity reflects its ability to process information, adapt to environmental changes, and transition between states. However, it remains unclear how schizophrenia (SZ) affects brain activity complexity, particularly its dynamic changes. This study aimed to investigate the abnormal patterns of brain activity complexity in SZ, their relationship with cognitive deficits, and the impact of antipsychotic medication. Forty-four drug-naive first-episode (DNFE) SZ patients and thirty demographically matched healthy controls (HC) were included. Functional MRI-based sliding window analysis was utilized for the first time to calculate weighted permutation entropy to characterize complex patterns of brain activity in SZ patients before and after 12 weeks of risperidone treatment. Results revealed reduced complexity in the caudate, putamen, and pallidum at baseline in SZ patients compared to HC, with reduced complexity in the left caudate positively correlated with Continuous Performance Test (CPT) and Category Fluency Test scores. After treatment, the complexity of the left caudate increased. Regions with abnormal complexity showed decreased functional connectivity, with complexity positively correlated with connectivity strength. We observed that the dynamic complexity of the brain exhibited the characteristic of spontaneous, recurring “complexity drop”, potentially reflecting transient state transitions in the resting brain. Compared to HC, patients exhibited reduced scope, intensity, and duration of complexity drop, all of which improved after treatment. Reduced duration was negatively correlated with CPT scores and positively with clinical symptoms. The results suggest that abnormalities in brain activity complexity and its dynamic changes may underlie cognitive deficits and clinical symptoms in SZ patients. Antipsychotic treatment partially restores these abnormalities, highlighting their potential as indicators of treatment efficacy and biomarkers for personalized therapy.

Overview of dendritic cells and related pathways in autoimmune uveitis.

Dendritic cells (DCs) play a crucial role in bridging innate and adaptive immune responses. They are widely distributed in various tissues and organs, including the eyes. In the ocular context, permanent DCs are present at the peripheral edge of the retina and the peripapillary area in an immature state. However, during the inflammatory process, DCs become activated and contribute to the development of uveitis. This review focuses on introducing the characteristics and status of DC-induced uveitis, exploring factors that can influence the status of DCs, and discussing feasible methods for treating DCs in both experimental autoimmune uveitis animal models and humans. It emphasizes the importance of further research on molecular pathways and signaling pathways that regulate the function of DCs. For example, investigating molecules such as cytotoxic T-lymphocyte-associated protein 4, which inhibits the B7-CD28 co-stimulatory interaction, can help improve immune homeostasis. The aim is to identify new therapeutic targets and develop targeted strategies for DCs, such as DC vaccine therapy or the use of immune modulators. These approaches can be tailored to the immune characteristics and disease manifestations of individual patients, enabling personalized treatment strategies. This may include the personalized design and precise medication of DC therapy, with the ultimate goal of improving treatment efficacy while minimizing adverse reactions.

Predictive model of castration resistance in advanced prostate cancer by machine learning using genetic and clinical data: KYUCOG-1401-A study

BackgroundThe predictive power of the treatment efficacy and prognosis in primary androgen deprivation therapy (ADT) for advanced prostate cancer is not satisfactory. The objective of this study was to integrate genetic and clinical data to predict castration resistance in primary ADT for advanced prostate cancer by machine learning (ML).MethodsClinical and single nucleotide polymorphisms (SNP) data obtained in the KYUCOG-1401-A study (UMIN000022852) that enrolled Japanese patients with advanced prostate cancer were used. All patients were treated with primary ADT. A point-wise linear (PWL) algorithm, logistic regression with elastic-net regularization, and eXtreme Gradient Boosting were the ML algorithms used in this study. Area under the curve for castration resistance and C-index for prognoses were calculated to evaluate the utility of the models.ResultsAmong the three ML algorithms, the area under the curve values to predict castration resistance at 2 years was highest for the PWL algorithm with all the datasets. Three predictive models (clinical model, small SNPs model, and large SNPs model) were created by the PWL algorithm using the clinical data alone, and 2 and 46 SNPs in addition to clinical data. C-indices for overall survival by the clinical, small SNPs, and large SNPs models were 0.636, 0.621, and 0.703, respectively.ConclusionThe results demonstrated that the SNPs models created by ML produced excellent prediction of castration resistance and prognosis in primary ADT for advanced prostate cancer, and will be helpful in treatment choice.

‘Everyone is Against me’: A Qualitative Study of Intimate Partner Violence Perpetration with Both Convicted and Voluntary Help-Seeking Men

ABSTRACT Intimate partner violence (IPV) significantly harms women globally, yet, research on perpetrator treatment efficacy is inconclusive. Understanding how perpetrators perceive their own perpetrations is crucial for effective prevention and treatment. This study examines how male IPV perpetrators describe their emotions and cognitions surrounding their violent acts, using Interpretative Phenomenological Analysis of interviews with seven convicted men, and six men who had sought treatment voluntarily. Two superordinate themes emerged: Aggression as a means to meet with unfulfilled psychological needs which encompasses how aggression is used to satisfy the need to gain control and protect the self, and Aggression as an automatic response which entails automatically reacting with aggression, for example due to perceiving the world through a hostile lens. These findings can increase our understanding of factors and dynamics related to precipitation and continuation of IPV perpetration, which, in turn, can be identified, assessed, and potential targets for intervention and prevention.

Novel biophysical skin biomarkers discriminate topical anti‐inflammatory treatments based on their potential for local adverse effects

AbstractBackgroundTopical corticosteroids (TCS) are efficacious treatments for inflammatory skin conditions, however, there is a risk of adverse effects; understanding how best to use these treatments is an unmet research priority shared by patients and healthcare professionals.ObjectivesTo develop non‐invasive biomarkers of local adverse effects to facilitate the optimisation of topical therapy.MethodsAn observer‐blind randomised within‐subject controlled trial in atopic dermatitis patients was undertaken (NCT04194814) comparing betamethasone valerate 0.1% cream (BMV) to a non‐steroidal anti‐inflammatory treatment, crisaborole 2% ointment (CRB). Participants underwent 4 weeks twice‐daily treatment with CRB on one forearm and BMV on the other (left/right randomised). Skin properties were assessed on days 1, 15, 29 of treatment and again on day 57, including imaging of skin microstructure using Optical Coherence Tomography (OCT) and Attenuated Total Reflectance (ATR)‐Fourier Transform Infrared (FTIR) spectroscopic assessment of stratum corneum molecular structure. The primary outcome was the difference in the change in epidermal thickness from days 1 to 29.ResultsThirty‐seven participants received the first dose, of which 32 completed the study (all 37 were included in the analysis). Pathologic epidermal thinning at day 29 was significantly greater (p < 0.0001) at sites treated with BMV (−31.66; 95% confidence interval: −35.31, −28.01 µm) compared to CRB (−13.76; −17.42, −10.10 µm). From a panel of exploratory biomarkers, superficial plexus depth and stratum corneum carboxyl group levels had the greatest ability to discriminate the effects of the TCS treatment (p < 0.0001).ConclusionsBMV induced 2.3x more pathologic epidermal thinning than CRB after 4 weeks of treatment, suggesting that CRB may be more appropriate for longer‐term, proactive‐based, treatment strategies where the risks of adverse effects are greatest. By monitoring treatment effects using OCT and ATR‐FTIR spectroscopy, two new non‐invasive biomarkers of skin health have been identified with the potential to help optimise future safe treatment strategies.

Outcome of regenerative endodontic procedures in delayed replanted immature permanent teeth with apical periodontitis: A retrospective study.

Regenerative endodontic procedures (REPs) is effective for treating young permanent teeth with pulp necrosis. However, its efficacy on delayed replanted avulsed teeth is unclear. This retrospective study aimed to assess the efficacy of REPs in treating delayed replanted immature permanent teeth with apical periodontitis. Avulsed teeth receiving REPs were systematically screened based on predetermined criteria. This study assessed the REP outcomes, postoperative periodontal healing, and overall treatment efficacy. Samples were grouped by REP outcomes and root development stage, with Fisher's exact tests used to compare outcomes among different groups. Among the included 17 teeth, 47.1% exhibited successful REPs and periodontal healing. Another 47.1%, due to replacement resorption or REP failure, were categorized as tooth survival. Healing of periapical lesions was observed in 88.2% of the cases, but only 41.2% demonstrated continued root development. Although differences were not significant (p = 0.05), teeth with continued root development had a higher rate of functional healing (85.7%) compared to those without (30%). Within the limitations of this study, REPs presented reliable outcomes for treating delayed replanted immature permanent teeth with apical periodontitis mainly in periapical lesion healing. Teeth with continued root development after REPs exhibited a higher rate of functional healing. Further investigation is required to explore potential synergies between REP outcomes and periodontal healing.

Single Cell Droplet-Based Efficacy and Transcriptomic Analysis of a Novel Anti-KLRG1 Antibody for Elimination of Autoreactive T Cells.

Progress in developing improvements in the treatment of autoimmune disease has been gradual, due to challenges presented by the nature of these conditions. Namely, the need to suppress a patient's immune response while maintaining the essential activity of the immune system in controlling disease. Targeted treatments to eliminate the autoreactive immune cells driving disease symptoms present a promising new option for major improvements in treatment efficacy and side effect management. Monoclonal antibody therapies can be applied to target autoreactive immune cells if the cells possess unique surface marker expression patterns. Killer cell lectin like receptor G1 (KLRG1) expression on autoreactive T cells presents an optimal target for this type of cell depleting antibody therapy. In this study, we apply a variety of in vitro screening methods to determine the efficacy of a novel anti-KLRG1 antibody at mediating specific natural killer (NK) cell mediated antibody-dependent cellular cytotoxicity (ADCC). The methods include single-cell droplet microfluidic techniques, allowing timelapse imaging and sorting based on cellular interactions. Included in this study is the development of a novel method of sorting cells using a droplet-sorting platform and a fluorescent calcium dye to separate cells based on CD16 recognition of cell-bound antibody. We applied this novel sorting method to visualize transcriptomic variation between NK cells that are or are not activated by binding the anti-KLRG1 antibody using RNA sequencing. The data in this study reveals a reliable and target-specific cytotoxicity of the cell depleting anti-KLRG1 antibody, and supports our droplet-sorting calcium assay as a novel method of sorting cells based on receptor activation.

Synergistic Chemo-Immunotherapy: Recombinant Fusion Protein-Based Surface Modification of NK Cell for Targeted Cancer Treatment

While traditional combination anticancer treatments have shown promising results, there remains significant interest in developing innovative methods to enhance and integrate chemotherapy and immunotherapy. This study introduces a recombinant fusion protein-based cell surface modification system that synergistically combines chemotherapy and immunotherapy into a single-targeted chemo-immunotherapy approach. A cell surface-modified protein composed of an antibody-specific binding domain and a cell-penetrating domain rapidly converts immune cells into chemo-immuno therapeutics by binding to antibodies on the surface of immune cells. Utilizing a non-invasive, non-toxic approach free of chemical modifications and binding, our system homogeneously transforms immune cells by transiently introducing targeted cytotoxic drugs into them. The surface-engineered immune cells loaded with antibody–drug conjugates (ADCs) significantly inhibit the growth of target tumors and enhance the targeted elimination of cancer cells. Therefore, NK cells modified by the cell surface-modified protein to incorporate ADCs could be expected to achieve the combined effects of targeted cancer cell recognition, chemotherapy, and immunotherapy, thereby enhancing their therapeutic efficacy against cancer. This strategy allows for the efficient and rapid preparation of advanced chemo-immuno therapeutics to treat various types of cancer and provides significant potential to improve the efficacy of cancer treatment.

Efficacy of herbicidal treatments in controlling weeds in sugar beet crop and their side effects on subsequent crops

Efficacy of herbicidal treatments in controlling weeds in sugar beet crop and their side effects on subsequent crops

Investigation of Advanced Nanoscale Biomaterials as Immune Modulators for Therapeutic Applications

Immunomodulatory agents play a crucial role in drug delivery by modulating the immune system's response to therapeutic agents, thereby enhancing treatment efficacy and safety. These agents can either stimulate the immune system to improve drug effectiveness, particularly in cancer and infectious diseases, or suppress it to prevent adverse reactions in conditions like organ transplantation and autoimmune diseases. The integration of immunomodulatory agents into drug delivery systems (DDS) enhances drug targeting, controls release, and optimizes pharmacokinetics. Advanced carriers such as nanoparticles and liposomes are employed to precisely deliver these agents, aligning with personalized medicine approaches to tailor treatments based on individual immune profiles. Despite their potential, challenges such as balancing immune modulation and addressing safety concerns remain. Ongoing research is focused on developing innovative DDS, improving targeting strategies, and identifying new immunomodulatory compounds to address these challenges. This abstract provides an overview of the role and impact of immunomodulatory agents in drug delivery systems and highlights the current trends and future directions in this evolving field.

The effect of fluence rate and wavelength on the formation of protoporphyrin IX photoproducts.

Photodynamic diagnosis and therapy (PDD and PDT) are emerging techniques for diagnosing and treating tumors and malignant diseases. Photoproducts of protoporphyrin IX (PpIX) used in PDD and PDT may be used in the diagnosis and treatment, making a detailed analysis of the photoproduct formation under various treatment and diagnosis conditions important.Spectroscopic and mass spectrometric analysis of photoproduct formation from PpIX dissolved in dimethyl sulfoxide were performed under commonly used irradiation conditions for PDD and PDT, i.e., wavelengths of 405 and 635nm and fluence rates of 10 and 100 mW/cm2. Irradiation resulted in the formation of hydroxyaldehyde photoproduct (photoprotoporphyrin; Ppp) and formyl photoproduct (product II; Pp II) existing in different quantities with the irradiation wavelength and fluence rate. Ppp was dominant under 635nm irradiation of PpIX, with a fluorescence peak at 673nm and a protonated monoisotopic peak at m/z 595.3. PpIX irradiation with 405nm yielded more Pp II, with a fluorescence peak at 654nm. A higher photoproduct formation was observed at a low fluence rate for irradiation with 635nm, while irradiation with 405nm indicated a higher photoproduct formation at a higher fluence rate.The photoproduct formation with the irradiation conditions can be exploited for dosimetry estimation and may be used as an additional photosensitizer to improve the diagnostics and treatment efficacies of PDD and PDT. Differences in environmental conditions of the present study from that of a biological environment may result in a variation in the photoproduct formation rate and may limit their clinical utilization in PDD and PDT. Thus, further investigation of photoproduct formation rates in more complex biological environments, including in vivo, is necessary. However, the results obtained in this study will serve as a basis for understanding reaction processes in such biological environments.

RIFAMPICIN‐LOADED NANO‐IN‐MICROPARTICLES (TROJAN PARTICLES) AS A PULMONARY DELIVERY SYSTEM FOR TUBERCULOSIS TREATMENT

The oral rifampicin (RIF) dosage forms possess various side effects and limited efficacy for tuberculosis treatment. Thus, this work developed the nano‐in‐microparticles containing RIF (trojan nRIF) as a novel pulmonary delivery system. The RIF‐loaded nanoparticles (nRIF) were prepared by self‐assembly polyelectrolyte complexation between lecithin and chitosan, whereas the trojan nRIF were formulated by spray‐drying method of nRIF and mannitol/maltodextrin. The nRIF had a spherical shape with sizes of 86‐126 nm, zeta potentials of 24‐39 mV, entrapment efficiencies of 44‐80%, and drug loading capacities of 13‐42%. The RIF release from nRIF occurred in two stages, the initially rapid release stage and the controlled release stage upto 96 h, followed the Higuchi model. The trojan nRIF possessed the mass median aerodynamic diameter of 3.7‐4.6 µm, fine particle fraction of 34‐40%, and alveolar fraction of 17‐21%. Compared to mannitol, maltodextrin was a superior carrier for nRIF, which yielded better aerodynamic properties and RIF was mainly stayed in the amorphous form. Moreover, using the scanning electron microscopy, the nano‐in‐microparticles were clearly observed with hollow structure. Finally, the trojan nRIF could preserve the physical properties of the encapsulated nRIF. In summary, the trojan nRIF could become a potential inhalation anti‐tuberculosis product.

Exploring the promising role of chitosan delivery systems in breast cancer treatment: A comprehensive review

Breast cancer presents a significant global health challenge, driving the development of novel treatment strategies for therapeutic interventions. Nanotechnology has emerged as a promising avenue for addressing this challenge, with Chitosan (CS) nanoparticles receiving prominence due to their unique characteristics and multitude of potential applications. This review provides a comprehensive overview of the role of Chitosan nanoparticles in breast cancer therapy. The review begins by emphasizing the prevalence and importance of breast cancer as a major health issue, underscoring the necessity for effective treatments. It then delves into the application of Chitosan nanoparticles in breast cancer therapy. One key aspect discussed is their role as carriers for anticancer drugs, enabling targeted delivery and improved cellular uptake. Furthermore, the review explores modified Chitosan nanoparticles and strategies for enhancing their efficacy and specificity in breast cancer treatment. It also examines Chitosan conjugates and hybrids, which offer innovative approaches for combination therapy. Additionally, metal and magnetic Chitosan nanoparticles are discussed spanning their capacity to assist in imaging, hyperthermia, as well as targeted drug delivery. In conclusion, the review summarizes the current research landscape regarding Chitosan nanoparticles for breast cancer therapy and offers insights into future directions. Overall, the review highlights the versatility, potential benefits, and future prospects of Chitosan nanoparticles in combating breast cancer.

Experimental Investigation of Bacterial Inactivation of Beef Using Indirect Cold Plasma in Cold Chain and at Room Temperature.

Pathogen contamination is a severe problem in maintaining food safety in the cold chain. Cold plasma (CP) is a novel non-thermal disinfection method that can be applied for the bacterial inactivation of food in appropriate contexts. Currently, research on CP used on food at cold chain temperatures is rare. This work investigated the bacterial inactivation effect of CP on beef at typical cold storage temperatures of 4 and -18 °C and room temperature (25 °C). The reactive species in CP were indirectly tested by evaluating O3, NO3- and NO2- in cold plasma-activated water (PAW), which indicated the highest concentrations of reactive species in CP at 25 °C and the lowest at -18 °C. The bactericidal efficacy of CP treatment against beef inoculated with Escherichia coli at -18 °C, 4 °C, and 25 °C was 30.5%, 60.1%, and 59.5%, respectively. The 4 °C environment was the most appropriate treatment for CP against beef, with the highest bactericidal efficacy and a minor influence on beef quality. The indirect CP treatment had no significant effect on the texture, color, pH, or cooking loss of beef at -18 °C. CP shows significant potential for the efficient decontamination of food at cold chain temperatures.

Claudin-4 remodeling of nucleus-cell cycle crosstalk maintains ovarian tumor genome stability and drives resistance to genomic instability-inducing agents.

AbstractDuring cancer development, the interplay between the nucleus and the cell cycle leads to a state of genomic instability, often accompanied by observable morphological aberrations. These aberrations can be controlled by tumor cells to evade cell death, either by preventing or eliminating genomic instability. In epithelial ovarian cancer (EOC), overexpression of the multifunctional protein claudin-4 is a key contributor to therapy resistance through mechanisms associated with genomic instability. However, the molecular mechanisms underlying claudin-4 overexpression in EOC remain poorly understood. Here, we altered claudin-4 expression and employed a unique claudin-4 targeting peptide (CMP) to manipulate the function of claudin-4. We found that claudin-4 facilitates genome maintenance by linking the nuclear envelope and cytoskeleton dynamics with cell cycle progression. Claudin-4 caused nuclei constriction by excluding lamin B1 and promoting perinuclear F-actin accumulation, associated with remodeling nuclear architecture, thus altering nuclear envelope dynamics. Consequently, cell cycle modifications due to claudin-4 overexpression resulted in fewer cells entering the S-phase and reduced genomic instability. Importantly, disrupting biological interactions of claudin-4 using CMP and forskolin altered oxidative stress cellular response and increased the efficacy of PARP inhibitor treatment. Our data indicate that claudin-4 protects tumor genome integrity by remodeling the crosstalk between the nuclei and the cell cycle, leading to resistance to genomic instability formation and the effects of genomic instability-inducing agents.Abstract FigureGraphical abstractClaudin-4 plays a crucial role in remodeling the cytoskeleton, particularly influencing nuclear architecture. This remodeling appears to act as a regulatory mechanism, limiting the progression of ovarian cancer cells into the S-phase and correlating with reduced genomic instability in ovarian tumors. Moreover, since olaparib treatment triggered a cellular oxidative response, it is likely that this claudin-4-mediated remodeling contributes to resistance against the effects of the PARP inhibitor.

Minning of Immuno-mitotic and GABAergic genes as potential biomarkers of glioblastoma: An integrated transcriptomic analysis

Glioblastoma (GBM) is a highly lethal Central Nervous System (CNS) tumor prevalent in both adults and children, exhibiting elevated rates of mortality and morbidity. Due to the heterogenous nature of GBM, coupled with its nonspecific symptoms underscore the imperative for innovative biomarkers to enhance prognosis and the development of efficacious therapeutic interventions. This bioinformatics study seeks to elucidate the culprit genes, both up-regulated and down-regulated, within the context of their functional relevance, through a comparative analysis of gene expression profiles in GBM and normal brain tissues. Deregulated genes were identified from two Gene Expression Omnibus (GEO) datasets, employing the GEO2R tool to analyze expression data from normal and GBM tissues. Subsequently, differences in expression of genes (DEGs) through functional enrichment analysis were conducted by DAVID to discern their functional implications. Further, Protein-Protein Interaction (PPI) networks were constructed to identify hub genes among the selected up-regulated and down-regulated genes, employing various bioinformatics tools. The impact of the selected hub genes on patient overall survival was investigated using the Gene Expression Profiling Interactive Analysis 2 (GEPIA2). Notably, the up-regulated hub genes KIF2C and TTK exhibited significant correlations with overall survival, implicating their potential as immuno-mitotic biomarkers. Conversely, GAD2, the sole down-regulated hub gene, emerged as a promising molecular target for GBM, given its association with GABAergic signaling and amino acid metabolism. Consequently, these findings suggest that KIF2C and TTK may serve as immune-mitotic biomarkers, while GAD2 could be explored as a molecular target for GBM therapy. Nevertheless, additional research is essential to unravel the precise mechanistic underpinnings of GBM.

The impact of inter-cycle treatment delays on overall survival in patients with advanced-stage ovarian cancer.

Chemotherapy forms the cornerstone of systemic treatment for advanced ovarian cancer, extending overall survival; however, drug-related toxicity can lead to treatment delays, potentially diminishing treatment efficacy. This study evaluated the impact of treatment delays on all-cause mortality of patients with ovarian cancer, to better inform decisions on patient management. This retrospective, population-based cohort study included 1517 women with advanced-stage ovarian cancer, receiving first-line adjuvant or neoadjuvant chemotherapy in 2014 and 2015. The frequency of inter-cycle delays >7 dayswas calculated using drug administration dates. Kaplan-Meier estimates were used to compare 2-year overall survival (OS) between patients who were delayed and those treated to schedule. Cox proportional hazards regression was used to investigate the impact of treatment delay on all-cause mortality. Inverse probability of treatment weighting propensity scores were used to adjust for confounding variables. Delays >7 days occurred in 35.3% of patients. Two-year OS probability was 62.7% in patients who experienced treatment delays >7 days (95% CI, 58.7-66.9) compared to 69.1% in those treated to schedule (95% CI, 66.2-72.0). Delays were not significantly associated with all-cause mortality when adjusted for confounders (HR 1.00 95% CI, 0.83-1.20, P = .9). Delays to chemotherapy treatment were not significantly associated with worsened survival in patients with advanced-stage ovarian cancer. These results can inform clinical decision making that prioritize toxicity management and quality of life for those treated with chemotherapy.