Therapeutic Hope Research Articles

Recent Advances in Immunotherapy for Breast Cancer: A Review.

Breast cancer is one of the most common malignant tumors in women in the world, and its incidence is increasing year by year, which seriously threatens the physical and mental health of women. Triple negative breast cancer (TNBC) is a special molecular type of breast cancer in which estrogen receptor, progesterone receptor and human epidermal growth factor receptor-2 are negative. Compared with other molecular types of breast cancer, triple-negative breast cancer (TNBC) has high aggressiveness and metastasis, high recurrence rate, lack of effective therapeutic targets, and usually poor clinical treatment effect. Chemotherapy was the main therapeutic means used in the past. With the advent of the immune era, immunotherapy has made a lot of progress in the treatment of triple-negative breast cancer (TNBC), bringing new therapeutic hope for the treatment of triple-negative breast cancer. This review combines the results of cutting-edge medical research, mainly summarizes the research progress of immunotherapy, and summarizes the main treatment methods of triple-negative breast cancer (TNBC) immunotherapy, including immune checkpoint inhibitors, tumor vaccines, adoptive immunotherapy and the application of traditional Chinese and western medicine. It provides a new idea for the treatment of triple negative breast cancer (TNBC).

Novel time-synchronized immune-guided partial tumor irradiation: Proof of principle trial

Background and purposeRadiotherapy for bulky tumors often results in palliation with suboptimal outcomes. The prognosis is worsened by immunosuppression caused by radio-chemotherapy, negatively impacting on survival. Novel Partial Tumor Irradiation (PTI) was designed to spare the Peritumoral Immune Microenvironment (PIM) and to be delivered synchronously with immune activity peaks, thus enhancing both local and distant tumor control through immunostimulation. Materials and methodsPresent proof-of-principle trial enrolled 26 patients with bulky tumors, comparing outcomes between treatments administered at immune activity peaks versus troughs. The primary endpoint was local-bystander and distal-abscopal response-rate. Secondary endpoints included overall-, progression-free-, cancer-specific survival, neoadjuvant and immunomodulatory potential. ResultsAll measured outcomes were significantly influenced by treatment-timing. The bystander and abscopal response rates were 77% and 41%, respectively. PTI significantly upregulated pro-inflammatory and cell-death-inducing pathways improving the efficacy of radiotherapy by highly complex tumors. ConclusionsThis study highlights the profound impact PTI can have on a highly palliative patient cohort previously deemed beyond therapeutic hope. With 41 % of these patients still alive after a median follow-up of 50 months, PTI offers a potential lifeline for those facing advanced, treatment-resistant cancers. This approach generated also distant immunogenic anti-tumor responses, offering a promising new avenue for the treatment of advanced cancers.

Ferroptosis and EMT resistance in cancer: a comprehensive review of the interplay.

Ferroptosis differs from traditional cell death mechanisms like apoptosis, necrosis, and autophagy, primarily due to its reliance on iron metabolism and the loss of glutathione peroxidase activity, leading to lipid peroxidation and cell death. The dysregulation of iron metabolism is a hallmark of various cancers, contributing to tumor progression, metastasis, and notably, drug resistance. The acquisition of mesenchymal characteristics by epithelial cells is known as Epithelial-Mesenchymal Transition (EMT), a biological process intricately linked to cancer development, promoting traits such as invasiveness, metastasis, and resistance to therapeutic interventions. EMT plays a pivotal role in cancer progression and contributes significantly to the complex dynamics of carcinogenesis. Research findings indicate that mesenchymal cancer cells exhibit greater susceptibility to ferroptosis compared to their epithelial counterparts. The induction of ferroptosis becomes more effective in eliminating drug-resistant cancer cells during the process of EMT. The interplay between ferroptosis and EMT, a process where epithelial cells transform into mobile mesenchymal cells, is crucial in understanding cancer progression. EMT is associated with increased cancer metastasis and drug resistance. The review delves into how ferroptosis and EMT influence each other, highlighting the role of key proteins like GPX4, which protects against lipid peroxidation, and its inhibition can induce ferroptosis. Conversely, increased GPX4 expression is linked to heightened resistance to ferroptosis in cancer cells. Moreover, the review discusses the implications of EMT-induced transcription factors such as Snail, Zeb1, and Twist in modulating the sensitivity of tumor cells to ferroptosis, thereby affecting drug resistance and cancer treatment outcomes. Targeting the ferroptosis pathway offers a promising therapeutic strategy, particularly for tumors resistant to conventional treatments. The induction of ferroptosis in these cells could potentially overcome drug resistance. However, translating these findings into clinical practice presents challenges, including understanding the precise mechanisms of ferroptosis induction, identifying predictive biomarkers, and optimizing combination therapies. The review underscores the need for further research to unravel the complex interactions between ferroptosis, EMT, and drug resistance in cancer. This could lead to the development of more effective, targeted cancer treatments, particularly for drug-resistant tumors, offering new hope in cancer therapeutics.

Targeting the Receptor at Synapse of Keratinocyte and Peripheral Nerve Ending: A Therapeutic Hope for Post-Burn Pruritus

Chronic itch or Pruritus is an unpleasant sensation that provokes the desire to scratch. In post burn patients, it is a significant health burden with few effective treatments. Pruritus is a common distressing consequence of postburn scars which affects burn survivors’ quality of life by causing sleep disturbance, daily activity impairment, and psychological problems. The mechanism of such abnormal scars with pruritus is not yet clear. The field of pruritus research is a dynamic field which involves neural component and various receptors at skin. The receptor present at the synapse of keratinocytes and peripheral nerve ending are responsible for itching. Many recent studies have worked to define the various receptors and the itch mediations in skin. However, considering that post-burn patients mainly report itch to be localized in the burn scars, spontaneous itch might be strongly based on peripheral input. The detailed characteristic and the factors for persistence of pruritus in post burn patients have not yet been clearly understood. Experimental evidences suggest that transient receptor potential (TRP) channels in skin and their expression patterns, activation mechanisms play regulatory roles in pruritus pathogenesis. In this article author collected the pruritus related data from post burn pruritus patients, isolated keratinocytes checked the receptor expression by immunocytochemistry and discussed the complex interplay between the central and peripheral factors that causes pruritus. It would be helpful to identify novel anti-pruritic agents that target the molecular itch pathogenesis pathways and the clinical assessment for burn patients with pruritus.

Ameliorative Effect of Vitamin E on Paraquat Induced Nephrotoxicity in Rat

The kidney is a very vital organ required for excretion of metabolic waste products in the body and when the kidney is damaged, this function is compromised. Paraquat is a toxicant that is known to have toxic injuries in different organs. Therefore, the aim of this study was to uncover the treatment effect of vitamin E in paraquat inflicted kidney injury. The experimental animals (male rats) were 200 and they were classified into 4 groups designated as A, B, C and D. The A served as the control group, B, C and D were test groups classified based on dose of paraquat administered. A was not treated with paraquat, B, C and D were treated with 0.02g, 0.04g and 0.06g of paraquat respectively every two weeks for three months. Each group mentioned had subgroups designated “0” and “VE”; “0” subgroups were subgroups not treated with vitamin E while “VE” were subgroups treated with 500mg of vitamin E. Treatment of vitamin E occurred weekly for one month. Both vitamin E and paraquat treatments occurred orally. After treatment period rats were sacrificed and blood sample collected via cardiac puncture for urea and creatinine assay. The results showed that there was no significant difference in urea levels among paraquat alone treated groups but there was a significant increase in creatinine levels among paraquat alone treated groups. There was a significant decrease in creatinine level after vitamin E treatment. This study has shown that vitamin E is a therapeutic hope for paraquat inflicted nephrotoxicity in rats.

A Molecular (Not Very Becoming) Picture of Stressed Arteries and Heart, with Some Therapeutic Hope

This Special Issue has focused on molecular mechanisms (vascular calcification, endothelial dysfunction, cardiac remodelling, inflammation, oxidative stress, etc [...].

Special Report: Measurement-Based Care—Using Data to Augment Psychotherapy

Special Report: Measurement-Based Care—Using Data to Augment Psychotherapy

Synthesis and application of spermine-based amphiphilic poly(β-amino ester)s for siRNA delivery.

Small interfering RNA (siRNA) can trigger RNA interference (RNAi) to therapeutically silence disease-related genes in human cells. The approval of siRNA therapeutics by the FDA in recent years generated a new hope in novel and efficient siRNA therapeutics. However, their therapeutic application is still limited by the lack of safe and efficient transfection vehicles. In this study, we successfully synthesized a novel amphiphilic poly(β-amino ester) based on the polyamine spermine, hydrophobic decylamine and 1,4-butanediol diacrylate, which was characterized by 1H NMR spectroscopy and size exclusion chromatography (SEC, Mn = 6000 Da). The polymer encapsulated siRNA quantitatively from N/P 5 on as assessed by fluorescence intercalation while maintaining optimal polyplex sizes and zeta potentials. Biocompatibility and cellular delivery efficacy were also higher than those of the commonly used cationic, hyperbranched polymer polyethylenimine (PEI, 25 kDa). Optimized formulations mediated around 90% gene silencing in enhanced green fluorescence protein expressing H1299 cells (H1299-eGFP) as determined by flow cytometry. These results suggest that spermine-based, amphiphilic poly(β-amino ester)s are very promising candidates for efficient siRNA delivery.

Characterization of Patients With Metastatic Renal Cell Carcinoma Experiencing Complete Response to First-line Therapies: Results From the International Metastatic Renal Cell Carcinoma Database Consortium.

Clinical trials have demonstrated higher complete response rates in the immuno-oncology-based combination arms than in the tyrosine kinase inhibitor arms in patients with metastatic renal cell carcinoma. We aimed to characterize real-world patients who experienced complete response to the contemporary first-line therapies. Using the International Metastatic Renal Cell Carcinoma Database Consortium, response-evaluable patients who received frontline immuno-oncology-based combination therapy or tyrosine kinase inhibitor monotherapy were analyzed. Baseline characteristics of patients and post-landmark overall survival were compared based on best overall response, as per RECIST 1.1. A total of 52 (4.6%) of 1,126 and 223 (3.0%) of 7,557 patients experienced complete response to immuno-oncology-based and tyrosine kinase inhibitor therapies, respectively (P = .005). An adjusted odds ratio for complete response achieved by immuno-oncology-based combination therapy (vs tyrosine kinase inhibitor monotherapy) was 1.56 (95% CI 1.11-2.17; P = .009). Among patients who experienced complete response, the immuno-oncology-based cohort had a higher proportion of non-clear cell histology (15.9% and 4.7%; P = .016), sarcomatoid dedifferentiation (29.8% and 13.5%; P = .014), and multiple sites of metastases (80.4% and 50.0%; P < .001) than the tyrosine kinase inhibitor cohort. Complete response was independently associated with post-landmark overall survival benefit in both the immuno-oncology-based and tyrosine kinase inhibitor cohorts, giving respective adjusted hazard ratios of 0.17 (95% CI 0.04-0.72; P = .016) and 0.28 (95% CI 0.21-0.38; P < .001). The complete response rate was not as high in the real-world population as in the clinical trial population. Among those who experienced complete response, several adverse clinicopathological features were more frequently observed in the immuno-oncology-based cohort than in the tyrosine kinase inhibitor cohort. Complete response was an indicator of favorable overall survival.

Platelet caspase‐1 and Bruton tyrosine kinase activation in patients with COVID‐19 is associated with disease severity and reversed in vitro by ibrutinib

BackgroundSeverity of coronavirus disease 2019 (COVID‐19) is often associated with thrombotic complications and cytokine storm leading to intensive are unit (ICU) admission. Platelets are known to be responsible for abnormal hemostasis parameters (thrombocytopenia, raised D‐dimers, and prolonged prothrombin time) in other viral infections through the activation of the nucleotide‐binding domain leucine repeat rich containing protein 3 inflammasome induced by signaling pathways driven by Bruton tyrosine kinase (BTK) and leading to caspase‐1 activation. ObjectivesWe hypothesized that caspase‐1 activation and the phosphorylation of BTK could be associated with the severity of the disease and that ibrutinib, a BTK inhibitor, could inhibit platelet activation. Methods and ResultsWe studied caspase‐1 activation by flow cytometry and the phosphorylation of BTK by Western blot in a cohort of 51 Afro‐Carribean patients with COVID‐19 disease (19 not treated in ICU and 32 treated in ICU). Patients with a platelet count of 286.7 × 109/L (69–642 × 109/L) were treated by steroids and heparin preventive anticoagulation. Caspase‐1 and BTK activation were associated with the severity of the disease and with the procoagulant state of the patients. Furthermore, we showed in vitro that the plasma of ICU patients with COVID‐19 was able to increase CD62P expression and caspase‐1 activity of healthy platelets and that ibrutinib could prevent it. ConclusionsOur results show that caspase‐1 and BTK activation are related to disease severity and suggest the therapeutic hope raised by ibrutinib in the treatment of COVID‐19 by reducing the procoagulant state of the patients.

Micropropagation and potential of bioactive compounds of saffron (Crocus sativus L.) for nutrition and health

To inquire about the possibility of durable valorization of saffron, this review highlights the different techniques of in vitro culture and varietal creation of this specie. Then, a reveal main component of saffron with some pharmacological activities that make this product a serious therapeutic hope. Saffron (Crocus sativus L.) is a sterile triploid geophyte that propagated by corms. To respond to the increasing global demand for saffron, it is necessary to expand the area under cultivation. Thus, in vitro techniques can produce a large quantity of propagating material in reduced time. It is well-known that saffron is traditionally used as a coloring or flavoring agent, but recent research showed its potential for health promotion. The interest components include crocin, crocetin, picrocrocin, and safranal have all demonstrated a wide range of use in medical field. Previous studies have reported that biological activities of saffron alleviates or prevents health problems such as stomach upset, cardiovascular disease, and depression. In addition, saffron is also promising in cancer prevention due to its antioxidant properties.

Multidisciplinary approach for a severe head burn caused by high-voltage electrical shock - a case report

In modern reconstructive medicine, personalized bone substitutes provide therapeutic hope for patients with non-standard bone defects. The study aims to present a description of a case of using a personalized bone substitute material, taking into account the vascular connections formed after a previous skin transplant. &#x0D; The 29-year-old patient was admitted to the plastic surgery department urgently after being electrocuted with high voltage. Due to extensive scalp burns, a skin graft was performed in the area of previously removed skin along with a charred skull bone vault. &#x0D; After a few months, the patient was qualified for cranioplasty with the use of personalized bone substitutes. The necessity to make cuts around the vascular connections present in the transplanted tissue was the main difficulty in the for the operator. &#x0D; The operation was successful and the recovery was uneventful. The patient was discharged home in good general and local condition. &#x0D; The presented case illustrates the need to take into account creating vascular connections with the use of personalized bone substitutes in patients after skin transplants.

Pyroptosis-related lncRNA pairs to estimate the molecular features and prognostic outcomes of pancreatic ductal adenocarcinoma

Pyroptosis is a form of programmed cell death associated with inflammatory alterations. However, the intrinsic mechanisms and underlying correlation of pyroptosis-related lncRNAs (PRLs) in pancreatic ductal adenocarcinoma (PDAC) remain unclear. The objective of the current research was to identify pyroptosis-related lncRNAs and a prognostic model to predict the prognosis of patients. We extracted pyroptosis-related lncRNAs to construct a risk model and validated them at Fudan University Shanghai Cancer Center. Crosstalk between lncRNA SNHG10 and GSDMD was found to regulate pyroptosis levels. A new algorithm was used to establish a 0 or 1 PRL pair matrix and prognostic model. Six pyroptosis-related lncRNA pairs were identified and utilized to construct a risk model. The low-risk groups exhibited better prognoses than the high-risk groups. The area under the curve (AUC) indicated extremely high accuracy, reaching 0.810 at 1 year, 0.850 at 2 years, and 0.850 at 3 years in the training set. Patients with different risk scores exhibited distinct metabolic, inflammatory, and immune microenvironments as well as tumor mutation landscapes. Additionally, 9 commonly used chemotherapeutic drugs exhibited different sensitivities between the high- and low-risk groups. To conclude, we propose that pyroptosis exhibits a close correlation with PDAC. Our risk model based on PRL pairs may be beneficial for the accurate estimation of prognostic outcomes, the immune microenvironment, and drug sensitivity, bringing therapeutic hope for patients with PDAC.

Radiopharmaceutical Treatments for Cancer Therapy, Radionuclides Characteristics, Applications, and Challenges.

Advances in the field of molecular biology have had an impact on biomedical applications, which provide greater hope for both imaging and therapeutics. Work has been intensified on the development of radionuclides and their application in radiopharmaceuticals (RPS) which will certainly influence and expand therapeutic approaches in the future treatment of patients. Alpha or beta particles and Auger electrons are used for therapy purposes, and each has advantages and disadvantages. The radionuclides labeled drug delivery system will deliver the particles to the specific targeting cell. Different radioligands can be chosen to uniquely target molecular receptors or intracellular components, making them suitable for personal patient-tailored therapy in modern cancer therapy management. Advances in nanotechnology have enabled nanoparticle drug delivery systems that can allow for specific multivalent attachment of targeted molecules of antibodies, peptides, or ligands to the surface of nanoparticles for therapy and imaging purposes. This review presents fundamental radionuclide properties with particular reference to tumor biology and receptor characteristic of radiopharmaceutical targeted therapy development.

Restoring type VII collagen in skin

New therapeutic hope is emerging for people with the rare inherited blistering skin disease recessive dystrophic epidermolysis bullosa (RDEB). Gurevich etal.1 have reported early-phase clinical trial data evaluating a topical herpes simplex virus 1 vector to restore missing type VII collagen in RDEB skin and heal wounds.

Multiple Sclerosis Biomarker Candidates Revealed by Cell-Type-Specific Interactome Analysis.

Multiple sclerosis (MS) is a demyelinating disorder that affects multiple regions of the central nervous system such as the brain, spinal cord, and optic nerves. Susceptibility to MS, as well as disease progression rates, displays marked patient-to-patient variability. To date, biomarkers that forecast differences in clinical phenotypes and outcomes have been limited. In this context, cell-type-specific interactome analyses offer important prospects and hope for novel diagnostics and therapeutics. We report here an original study using bioinformatic analysis of MS data sets that revealed interaction profiles as well as specific hub proteins in white matter (WM) and gray matter (GM) that appear critical for disease mechanisms. First, cell-type-specific interactome analyses suggested that while interactions within the WM were focused on oligodendrocytes, interactions within the GM were mostly neuron centric. Second, hub proteins such as APP, EGLN3, PTEN, and LRRK2 were identified to be differentially regulated in MS data sets. Lastly, a comparison of the brain and peripheral blood samples identified biomarker candidates such as NRGN, CRTC1, CDC42, and IFITM3 to be differentially expressed in different types of MS. These findings offer a unique cell-type-specific cell-to-cell interaction network in MS and identify potential biomarkers by comparative analysis of the brain and the blood transcriptomics. From a study design and methodology perspective, we suggest that the cell-type-specific interactome analysis is an important systems science frontier that might offer new insights on other neurodegenerative and brain disorders as well.

Prognostic Impact of Poliovirus Receptor Expression (PVR) (CD155) in Context to FLT3-ITD and NPM1 Mutation Status at Egyptian Acute Myeloid Leukemia

Background: Acute myeloid leukemia is a heterogeneous hematological malignancy with diversity in molecular, phenotypic and genetic alteration. Accurate assessment of prognosis is mandatory to reduce relapse, changing treatment related mortality, decision making for appropriate therapy protocols. Aim: A case control observational analytical study to assess the prognostic value of poliovirus (CD155) in acute myeloid leukemia and its significant in-patient stratification. Subject & Methods: 100 newly diagnosed de novo AML selected from oncology center, Mansoura University. Measurement of PVR (CD155) by multiparameter flow cytometry in addition to cytogenetic and molecular stratification. Results: Statistical stratification according to median cut off CD155 > 5.35. Higher expression was associated with an increased risk of death and relapse, LDH. While lower expression is associated with longer OS & DFS. Cox regression with univariate analysis revealed that LDH, molecular stratification, CD155 were significant risk factors for shorter OS, while positive expression of CD16, CD56 AML M3 were significantly associated with longer survival. Multivariate analysis revealed that CD155 was a significant risk factor for shorter OS. Conclusion: Variability in expression of CD155 in AML patients due to dual costimulatory and inhibitory function, high expression associated with tumor bulk and progression, short OS, increased relapse rate. Cox regression analysis shows its independent risk factor. It could be implemented in routine laboratory for risk stratification into low, high risk that needs more therapeutic modalities with new immunotherapy. In future could be targeted therapy such as PDL, CTLA-4 and open more therapeutic hope for those patients.

Medicine-food herb: Angelica sinensis, a potential therapeutic hope for Alzheimer's disease and related complications.

Alzheimer's disease (AD) is a progressive neurodegenerative disease, which has brought a huge burden to the world. The current therapeutic approach of one-molecule-one-target strategy fails to address the issues of AD because of multiple pathological features of AD. Traditionally, the herb of Angelica sinensis (AS) comes from the root of an umbrella plant Angelica sinensis (Oliv.) Diels. As a typical medicine-food herb, studies have shown that AS can alleviate AD and AD-complications by multiple targets through the various foundations of pharmaceutical material and dietary supply basis. Therefore, this review summarizes the pharmacological effects of AS for the treatment of AD and AD-complications for the first time. AS contains many effective components, such as ligustilide, z-ligustilide, n-butylidenephthalide, α-pinene, p-cymene, myrcene, ferulic acid, vanillic acid and coniferyl ferulate. It is found that AS, AS-active compounds and AS-compound recipes mainly treat AD through neuroprotective, anti-inflammation, and anti-oxidant effects, improving mitochondrial dysfunction, anti-neuronal apoptosis, regulating autophagy, regulating intestinal flora and enhancing the central cholinergic system, which shows the multi-component and multi-target effect of AS. The role of dietary supplement components in AS for AD intervention is summarized, including vitamin B12, folic acid, arginine, and oleic acid, which can improve the symptoms of AD. Besides, this review focuses on the safety and toxicity evaluation of AS, which provides a basis for its application. This review will provide further support for the research on AD and the application of medicine-food herb AS in a healthy lifestyle in the future.

Cytokines in Schizophrenia: Predisposing Factors and Inflammatory Responses

Schizophrenia is a multifactorial disease that may be triggered by environmental disorders, mental stress, or physical illness in a person who is genetically predisposed to it. Recent research has extremely evaluated the role of inflammatory cytokines in schizophrenia. The current study attempted to find any association between cytokines and schizophrenia. This narrative study was conducted through a literature review in Scopus, PubMed, and Web of Science databases using keywords related to schizophrenia and cytokines without any time limitation. This review focused on discussing the relationship between various symptoms of disease and cytokine levels. Environmental factors such as embryonical infections were found to be associated with alternations in mothers’ blood cytokines and further effects on schizophrenia probability in children. Heritable factors including disrupted-in-schizophrenia 1 (DISC1) and neuregulin 1 (NRG1) genes were shown to be linked with immunological responses, as well as Toll-like receptors or AKT1/p13k activation and following alternations in the cytokine profile. Based on the findings, the cytokines and inflammatory responses of the body were reported to be involved in many psychological disorders and schizophrenia. Various interleukins (ILs), as well as IL-6, IL-8, and IL-2R are known to be associated with the severity of schizophrenia symptoms. Although various data exist regarding different cytokines and their association with schizophrenia, no study has so far formulated research fields on specific types of cytokines that have the potential to be further studied for therapeutic hope.

The Role of CDK4 in the Pathogenesis of Pancreatic Cancer.

Pancreatic cancer (PC) continues to have the lowest overall survival and the lack of effective early diagnosis. Cyclin-dependent kinase 4 (CDK4) plays a fundamental role in the orderly progression of the cell cycle, binding to cyclin D to promote the progression through the G1/2 transition. The inhibition of CDK4/6 has therefore gained substantial interest in the hope of new and effective therapeutics in multiple cancers, such as advanced metastatic breast cancer. While the use of these agents is encouraging, their potential is yet to be fully explored. In this study we used the GLOBOCAN database to understand the most recent epidemiology of PC, Human Protein Atlas and KEGG to highlight the role, prevalence, and significance on patient survival of CDK4 in PC. We found that CDK4 cannot be used as prognostic in PC and no significant differences were observed between CDK4 expression and the patient’s clinical status, though larger studies, especially concerning CDK4 protein expressions, are required for a more thorough understanding. The use of CDK4/6 inhibitors in PC is still in clinical trials. However, due to only modest improvements observed in the use of single-agent therapies, efforts have focused on combinatorial approaches.