Current Treatment Research Articles

Assessment of Optimal Treatment Strategies and Their Outcomes in T3N1 Rectal Cancers.

Background:This study compares the outcomes of a surgery first vs a neoadjuvant treatment strategy in T3N1M0 rectal cancers. Methods:This was a single-centre retrospective cohort study of patients admitted for curative treatment of T3N1 rectal cancer. Patients with pre-treatment T3N1 and pathological T3N1 disease were included in the study. Patients were divided into two groups depending on whether they had surgery or neoadjuvant therapy as their initial phase of treatment. Primary outcome measures were local recurrence and distant recurrence. Secondary outcomes were disease-free survival (DFS) and overall survival (OS). Tabulated results were analyzed with appropriate statistical tests. Results:One hundred and ten patients were initially selected. Fourty-eight were finally included after excluding patients who did not meet the staging criteria or were not eligible for curative treatment. Twenty-nine patients underwent surgery, and 19 patients with neoadjuvant therapy as their first treatment. No local recurrence was noted in either group, with a distant recurrence noted in group 2 (6.9%) and group 1 (5.26%) cases among the surgery-first and neoadjuvant-first groups, respectively. Disease-free survival and overall survival were 29.5 and 30 months for the surgery-first group and 22 and 22 months for the neo-adjuvant group, respectively. Conclusions:Outcomes in the surgery-first group were non-inferior to that of the neoadjuvant group. A threatened circumferential resection margin (CRM) on pretreatment staging warrants neoadjuvant therapy to ensure an R0 resection. Extramural vascular invasion (EMVI), being a negative prognostic factor, doesn't preclude a surgery-first approach.

Menstrual Blood-Derived Endometrial Stem Cells Ameliorate Ovarian Senescence by Relieving Oxidative Stress-Induced Inflammation.

Senescence is a degenerative process that occurs with ageing, and in the female reproductive system, senescence occurs earlier in the ovaries than in other tissues and organs, which implies a decrease in oocyte quality and exhaustion of the primordial follicular pool, leading to impaired ovarian function and an inability to maintain normal fertility. Unfortunately, the development of curative and effective treatments for ovarian senescence is still a considerable challenge. Currently, mesenchymal stem cells (MSCs)-based therapies for treating various refractory diseases, especially ovarian dysfunction, have been extensively studied and confirmed. However, the mechanisms by which MSCs improve ovarian senescence are not yet clear. Therefore, in this study, a mouse ageing model was generated via the intraperitoneal injection of a D-galactose (D-gal) solution, and the effects of menstrual blood-derived endometrial stem cells (MenSCs) transplantation on the ovarian follicle count, fibrosis level, and degree of apoptosis were evaluated. Subsequently, an ovarian granulosa cell ageing model was induced with H2O2, and CCK-8 assays, flow cytometry, mitochondrial membrane potential analysis and Western blotting were subsequently performed to further investigate the potential mechanism by which MenSCs ameliorate cellular oxidative damage. Overall, our findings demonstrated that MenSCs treatment can increase the cellular antioxidant capacity by activating the NRF2/HO-1 signalling pathway and further ameliorate the inflammatory ovarian microenvironment, apoptosis and dysfunction in ageing mice. These results provide reliable evidence and support for MenSCs-based therapy for ovarian senescence.

The outcome of haematopoietic stem cell transplantation in a patient with STAT1 gain-of-function: a case report

Background: The human signal transducer and activator of transcription 1 (STAT1) is a latent cytoplasmic transcription factor and one of seven members of the STAT family. Autosomal dominant (AD) STAT1 gain-of-function (GOF), characterized by enhanced phosphorylation of the tyrosine-701 residue and STAT1 activation, is commonly associated with chronic mucocutaneous candidiasis (CMCC), immunodeficiency, aneurysms, malignancies, and autoimmune phenomena. The best management strategies for patients with STAT1 GOF remain unclear. Typically, the standard care includes supportive treatments such as antimicrobial prophylaxis, either alone or combined with immunoglobulin replacement therapy. Biological therapies such as JAK inhibitors have been shown to alleviate symptoms of infection and autoimmune disorders in patients with STAT1 GOF mutations. However, there is a lack of long-term outcome data for JAK inhibition. Hematopoietic stem cell transplantation (HSCT) is an alternative treatment option for a subset who experience a persistent disease course despite conventional therapy. However, the effectiveness of HSCT for this condition is not yet well established. Methods: Our patient’s medical records were analyzed retrospectively, including her medical history. Results: We present the outcome of HSCT performed on a 27-year-old female with STAT1 GOF, conducted as a treatment for acute myeloid leukemia (AML). Conclusion: HSCT may serve as an alternative and potentially curative treatment for certain STAT1 GOF patients with progressive, life-threatening conditions that do not respond to conventional therapies. Additional research is needed to improve the management of these patients. Statement of Novelty: We present a novel case study of HSCT as a treatment for AML in a 27-year-old patient with STAT1 GOF, highlighting the potential for curative outcomes in progressive, life-threatening conditions unresponsive to conventional therapies. This case contributes to the limited body of evidence supporting the efficacy and challenges of HSCT in STAT1 GOF patients.

ACSL1 improves pulmonary fibrosis by reducing mitochondrial damage and activating PINK1/Parkin mediated mitophagy

Pulmonary fibrosis is a chronic interstitial lung disease with no curative therapeutic treatment, leading to significant mortality. The aims of this study were to investigate the regulatory mechanisms of mitophagy in the progression of pulmonary fibrosis. Through bioinformatics analysis, we identified the downregulation of long-chain fatty acyl-CoA synthetase 1 (ACSL1) as being associated with the severity of pulmonary fibrosis. A pulmonary fibrosis model was established through bleomycin (BLM) exposure both in vivo and in vitro. Mitoquinone (MitoQ) pretreatment significantly decreased redox damage, stabilized mitochondrial membrane potential (MMP), improved mitochondrial dynamics, and activated PINK1/Parkin-mediated mitophagy, thereby alleviating pulmonary fibrosis. In vitro, overexpression of ACSL1 mitigated mitochondrial damage and restored PINK1/Parkin-mediated mitophagy under BLM exposure. In contrast, ACSL1 inhibition exacerbated pulmonary fibrosis, and these adverse effects could not be reversed by MitoQ treatment. Taken together, our study reveals a novel mechanism underlying the pathogenesis of pulmonary fibrosis and suggests a potential therapeutic target for its treatment.

Perindopril Ameliorates Sodium Valproate-Induced Rat Model of Autism: Involvement of Sirtuin-1, JAK2/STAT3 Axis, PI3K/Akt/GSK-3β Pathway, and PPAR-Gamma Signaling

Background and Objectives: Autism is a developmental disability characterized by impairment of motor functions and social communication together with the development of repetitive or stereotyped behaviors. Neither the exact etiology or the curative treatment of autism are yet completely explored. The goals of this study were to evaluate the possible effects of perindopril on a rat model of autism and to elucidate the possible molecular mechanisms that may contribute to these effects. Materials and Methods: In a rat model of sodium valproate (VPA)-induced autism, the effect of postnatal administration of different doses of perindopril on growth and motor development, social and repetitive behaviors, sirtuin-1, oxidative stress and inflammatory markers, PI3K/Akt/GSK-3β pathway, JAK2/STAT3 axis, and PPAR-gamma signaling in the hippocampal tissues were investigated. The histopathological and electron microscopic changes elicited by administration of the different treatments were also investigated. Results: Perindopril dose-dependently combatted the effects of prenatal exposure to VPA on growth and maturation, motor development, and social and repetitive behaviors. In addition, the different doses of perindopril ameliorated the effects of prenatal exposure to VPA on sirtuin-1, oxidative stress and inflammatory markers, PI3K/Akt/GSK-3β pathway, JAK2/STAT3 axis, and PPAR-gamma signaling. These effects had a mitigating impact on VPA-induced histopathological and electron microscopic changes in the hippocampal tissues. Conclusions: Perindopril may emerge as a promising agent for amelioration of the pathologic changes of autism spectrum disorders.

Oncologic outcomes and trends in each colon cancer location and stages over the last two decades: insights from the SEER registry.

The main purpose of the study is to comprehensively evaluate population-level survival disparities stage-by-stage, according to specific anatomical colon segments, and based on prognosis as defined by lymph nodes among patients who have undergone curative resection for non-metastatic colon cancer. The study was conducted from the Surveillance Epidemiology and End Result (SEER) program from the USA. Patients who underwent surgery for colon adenocarcinoma between 2000 and 2019 were identified. Demographics and clinical and pathologic factors were compared amongst each other according to different colon segments, stages, and time periods. A total of 482,672 patients were identified and 195,105 of them met the inclusion criteria. Patients with proximal cancers were significantly older, more likely to be female, had a higher number of lymph nodes, and node positivity (p < 0.001). During the study period, an almost 10% improvement in overall survival rate was observed at 3 and 5years for each colon site and stage (p < 0.05). The study's findings revealed a notable improvement in overall and cancer-specific survival rates across all colon segments and stages in patients who underwent curative treatment for non-metastatic primary colon cancer from a nationwide database.

Antifungal Activity of Citrus Essential Oil in Controlling Sour Rot in Tahiti Acid Lime Fruits

Sour rot, caused by Geotrichum citri-aurantii, is a significant post-harvest disease in citrus, resulting in economic losses due to the lack of effective fungicides. This study investigates the antifungal activity of citrus essential oils in controlling sour rot in Tahiti acid lime fruits. Essential oils were extracted via hydrodistillation with chemical composition analyzed by CG-MS and tested in vitro and in vivo. In vitro assays evaluated mycelial growth inhibition at 2 to 32 µL mL−1 concentrations. In vivo trials involved preventive and curative treatments on artificially inoculated fruits stored at 25 °C ± 2, and the results showed that Pera IAC sweet orange oil, at 32 µL mL−1, reduced disease severity by 96% in curative treatments. In contrast, Late IAC 585 willowleaf mandarin oil demonstrated moderate inhibition (44%) at the highest concentration in vitro. The oils did not affect key fruit quality parameters such as juice yield and total soluble solids. These findings suggest that citrus essential oils could be natural alternatives to synthetic fungicides for post-harvest sour rot management, combining effectiveness with maintaining fruit quality.

Impact of social determinants of health on hepatocellular carcinoma surveillance, treatment, and health care costs.

The impact of clinical factors and social determinants of health on treatment patterns and health care costs among patients with HCC is unknown. Using 100% Medicare Fee-For-Service claims and a commercial multipayor claims database, we identified patients diagnosed with HCC from January 1, 2017, to December 31, 2020. Surveillance receipt was defined 12 months prior to HCC diagnosis, whereas treatment and health care costs were assessed post-HCC diagnosis. Multinomial logistic regression was used to assess the association between demographics, social determinants of health, and surveillance or HCC treatment. Multivariable generalized linear regression was used to identify factors associated with total health care costs. Of the 32,239 patients with HCC (mean age 68 y, 67% male, 73% White), 70% received surveillance and only half (51%) received any treatment. Curative treatment receipt was higher among those with prior surveillance (24% with CT/MRI and 18% with ultrasound vs. 9% with no surveillance). Curative treatment was independently associated with HCC surveillance and inversely associated with Black race, lower education level, and diagnosis in the year 2020 (COVID-19 year). Higher health care costs were independently associated with Black race, low English proficiency, living alone, and diagnosis in 2018-2020, and inversely associated with CT/MRI-based surveillance. Race and social determinants of health were independently associated with curative treatment receipt and health care costs. Increasing access to high-quality HCC surveillance may improve treatment receipt and reduce health disparities among patients with HCC.

P206 How is the efficacy of patient selection criteria for adjuvant pembrolizumab after curative surgical treatment of clear cell renal cell carcinoma with intermediate to high risk of recurrence? A real-life data analysis from single institutional experience

P206 How is the efficacy of patient selection criteria for adjuvant pembrolizumab after curative surgical treatment of clear cell renal cell carcinoma with intermediate to high risk of recurrence? A real-life data analysis from single institutional experience

Herbal Components for the Treatment of Liver Disorders: Advances and Prospective

Abstract: The situation is made worse by the absence of detailed treatment plans for liver disease, a dangerous illness. The current liver disease treatments are insufficient, and their long-term usage is prevented by systemic toxicity. Since the toxicity factor seems to be on the lower end of the spectrum, herbal remedies have been utilized for ages to treat liver ailments. This article focuses on providing insight into liver diseases along with the herbal components that are used nowadays for efficiently treating them. The given herbal components glycyrrhizin, quercetin, curcumin, silymarin, and Phyllantus niruri have proven to be efficacious in treating liver diseases with no or bare minimum side effects. The liver diseases discussed in this review article include alcoholic liver disease, non-alcoholic fatty liver disease, hepatitis C, hepatitis B, hemochromatosis as well and auto-immune hepatitis. After summarization, it is concluded that these herbal components are proven to be effective in the treatment of liver diseases, and various research as well as studies have been conducted for the same.

Decorin-armed oncolytic adenovirus promotes natural killers (NKs) activation and infiltration to enhance NK therapy in CRC model

Colorectal cancer (CRC) is a prevalent malignant tumor of the gastrointestinal system, with the third and second highest incidence and mortality rates globally in 2020, respectively. Immunotherapy has developed rapidly in recent years. Natural killer (NK) cells have received increasing attention in the field of tumor immunotherapy due to their recognition and killing tumor cells without the limitations of major histocompatibility complexes. However, constraints within the tumor microenvironment that impede the infiltration and proliferation of NK cells result in poor efficacy of NK cell therapy for solid tumors. Oncolytic viral therapy is an immunogenic treatment with the potential to enhance anti-tumour immune responses and promote immune cell infiltration. In this study, we synergistically combine NK cells with an oncolytic adenovirus carrying Decorin (rAd.DCN) for the treatment of colorectal cancer (CRC) in a xenograft mouse model. By using Flow cytometry, real-time quantitative PCR and Calcein-AM release assay, we found that rAd.DCN could effectively promote proliferation, activation and degranulation of NK cells, up-regulate expression and secretion of NK cell killing activity-related factors, and enhance their killing activity. The efficacy is better than that of the blank control oncolytic virus rAd.Null. Combined treatment significantly inhibited tumor growth, increased the number of NK cells in peripheral blood, promoted the killing function of NK cells, and increased the expression levels of perforin and IFN-γ. At the same time, more NK cells were recruited to infiltrate tumor tissue. Our study established the feasibility of combination NK cells and oncolytic adenovirus application, thus expanding the scope of potentially curative treatments for NK cells in CRC.

P261 A Phase 1b-2 study of chemoradiotherapy combined with Nivolumab and Ipilimumab as bladder sparing curative treatment for muscle Invasive bladder cancer: The CRIMI study

P261 A Phase 1b-2 study of chemoradiotherapy combined with Nivolumab and Ipilimumab as bladder sparing curative treatment for muscle Invasive bladder cancer: The CRIMI study

Histology-Tailored Approach to Soft Tissue Sarcoma.

Soft tissue sarcomas are a diverse and heterogeneous group of cancers of mesenchymal origin. Each histological type of soft tissue sarcoma has unique clinical particularities, which makes them challenging to diagnose and treat. Multidisciplinary management of these rare diseases is thus key for improved survival. The role of surgery has been well established, and it represents the cornerstone curative treatment for soft tissue sarcomas. To date, local recurrence is the leading cause of death in low-grade sarcomas located at critical sites, and distant metastasis in high-grade sarcomas, regardless of the site of origin. Management must be tailored to each individual histologic type. We describe the most common types of extremity, trunk, abdominal, and retroperitoneal soft tissue sarcoma along with characteristics to consider for optimized management.

Anastomotic leakage following surgical resection in the upper gastrointestinal tract

Surgical resection is the consistent component of curative treatment strategies for primary malignant diseases of the stomach and the esophagus. The placement of anastomoses for the necessary reconstruction still accounts for substantial morbidity and in the case of afailure to rescue also for mortality, especially for esophagojejunostomy and esophagogastrostomy. The diagnostics of anastomotic leakage routinely involve computed tomography and endoscopy and timely performance appears to be essential. Endoscopy can simultaneously initiate the essential treatment step. Amajor reason for the improvement of postoperative outcomes after resection in the upper gastrointestinal tract in the last decades is the successful and mostly endoscopically performed management of anastomotic leakage, whereby different endoscopic treatment options are now available. Endoscopic vacuum therapy has become established as the standard, normally with an endoscopic vacuum sponge technique but is also now supplemented by acombination system of vacuum sponge and stent. Furthermore, afoil-coated multiple lumen nasogastric tube represents another available option, which can possibly especially be used as aprophylactic measure. The longest established endoscopic therapy option for anastomotic leaks, the endoluminal metal stent, has been replaced as the standard by the vacuum treatment but is still used in suitable situations. Additionally, there are endoscopic suture devices that are currently only used very occasionally. Surgical revision is always available as treatment escalation but is only recommended for very early occurrences and possibly technically related anastomotic leakage and in the case of failure of endoscopic treatment. This article describes and summarizes the diagnostics and treatment of anastomotic leakages after surgical procedures of the upper gastrointestinal tract.

The Clinical Impact of the Systemic Immune-inflammation Index in Esophageal Cancer Patients Receiving Curative Treatment.

The systemic immune-inflammation index (SII) is a calculated biomarker developed to predict the prognosis of malignant tumors. This study evaluated the influence of the SII in patients with esophageal cancer (EC) who underwent curative resection. Patients who underwent radical esophagectomy and lymph node dissection for EC were enrolled. The SII was calculated as follows: neutrophil count (cell/mm3) × platelet count (cell/mm3 ×103)/lymphocyte count (cell/mm3). The SII, patient characteristics, overall survival (OS), and recurrence-free survival (RFS) were assessed. A total of 180 patients were included in this study. The cutoff value of the SII was set at 500 according to previous studies. Of the 180 patients, 100 were classified into the SII-high group and 80 into the SII-low group. The 3- and 5-year OS rates were 59.0% and 54.0%, respectively, in the SII-high group and 80.0% and 75.0%, respectively, in the SII-low group, showing significant differences between the groups (p=0.001). A multivariate analysis for the OS demonstrated that the SII was an independent prognostic factor (hazard ratio=2.333, 95% confidence interval=1.411-3.860, p<0.001), with similar results obtained for the RFS. Furthermore, hematological recurrence was significantly higher in the SII-high group than in the SII-low group (36.0% vs. 17.5%, p=0.006). The preoperative SII was an independent prognostic factor for OS and RFS in patients with EC who underwent curative resection. Thus, the SII can be a useful marker for the treatment and management of EC.

Tumor Necrosis Alpha (TNF-α) Antagonists Used in Chronic Inflammatory Rheumatic Diseases: Risks and their Minimization Measures.

Tumor necrosis factor alpha (TNF- α) inhibitors are widely employed for the management of chronic inflammatory rheumatism. However, their usage carries significant risks, including site and infusion reactions, serious infections, malignancy, heart failure autoimmune and demyelinating disorders. These risks are comprehensively outlined in risk management plans (RMPs) associated with these molecules. RMP provides information on the safety profile of a medicinal product as well as the measures that will be taken to minimize risks; these are known as risk minimization measures. These measures are divided into routine measures related to elements, such as the summary of product characteristics, labeling, pack size, package leaflet, or legal supply status of the product, while additional measures may include educational programs, including tools for healthcare providers and patients, controlled access or pregnancy prevention programs, among others. Additional measures can consist of one or more interventions that need to be implemented in a sustainable way in a defined target group, while respecting the timing and frequency of any intervention and procedures to reach the target population. An evaluation of the effectiveness of these measures is required to determine whether or not an intervention has been effective. This comprehensive review offers an in-depth exploration of the current treatment, uses, and associated risks of TNF-α inhibitors. Additionally, it provides a detailed account of risk minimization measures and risk management practices while shedding light on their real-world implementation and effectiveness.

Treatment Considerations to Overcome the Barriers Associated with Skin Cancer Targeting

: Skin cancer is a prevalent and diverse group of malignancies affecting the skin, with three primary types: basal cell carcinoma, squamous cell carcinoma, and melanoma. Each subtype varies in terms of its histological origin, behavior, and potential for metastasis. Despite advances in treatment, skin cancer poses challenges due to biological barriers that hinder drug delivery, multidrug resistance mechanisms that limit treatment effectiveness, and the complex interplay of genetic alterations driving tumorigenesis. Current treatment strategies encompass a spectrum of approaches, including chemotherapies, immunotherapies, gene therapies, and innovative techniques such as photothermal therapy, iontophoretic therapy, electroporation therapy, microneedle array therapy, and nanotechnology- based treatments. The latter involves liposomes, niosomes, carbon nanotubes, dendrimers, hydrogels, and gold nanoparticles, all tailored to enhance drug delivery and therapeutic efficacy. Additionally, herbal drug-based therapy harnesses the potential of natural compounds to target various aspects of skin cancer progression. This review provides an overview of skin cancer types, challenges in treatment, and an extensive exploration of current therapeutic strategies, highlighting the everevolving landscape of innovative approaches that promise to transform how skin cancer is managed.

Angiogenesis and Pancreatic Cancer: Novel Approaches to Overcome Treatment Resistance.

Pancreatic cancer (PCa) is acknowledged as a significant contributor to global cancer- related mortality and is widely recognized as one of the most challenging malignant diseases to treat. Pancreatic ductal adenocarcinoma (PDAC), which is the most common type of PCa, is highly aggressive and is mostly incurable. The poor prognosis of this neoplasm is exacerbated by the prevalence of angiogenic molecules, which contribute to stromal stiffness and immune escape. PDAC overexpresses various proangiogenic proteins, including vascular endothelial growth factor (VEGF)-A, and the levels of these molecules correlate with poor prognosis and treatment resistance. Moreover, VEGF-targeting anti-angiogenesis treatments are associated with the onset of resistance due to the development of hypoxia, which in turn induces the production of angiogenic molecules. Furthermore, excessive angiogenesis is one of the hallmarks of the second most common form of PCa, namely, pancreatic neuroendocrine tumor (PNET). In this review, the role of angiogenesis regulators in promoting disease progression in PCa, and the impact of these molecules on resistance to gemcitabine and various therapies against PCa are discussed. Finally, the use of anti-angiogenic agents in combination with chemotherapy and other targeted therapeutic molecules is discussed as a novel solution to overcome current treatment limitations in PCa.

In vivo biocontrol potential of Bacillus plant growth-promoting rhizobacteria against pectinolytic plant pathogens.

Bacillus is well known for producing a wide range of compounds that inhibit microbial phytopathogens. From this perspective, we were interested in evaluating the biocontrol potential of 5 plant growth-promoting rhizobacteria Bacillus species (PGPR-Bacillus) on 21 microbial pectinolytic plant pathogens isolated from previous studies. Phytopathogenicity and in vivo biocontrol potential of PGPR curative and preventive treatments were investigated from this angle. Overall, the pathogenicity test on healthy tomato, zucchini, and mandarin showed low rot to no symptoms for all PGPR strain culture treatments. Conversely, zucchini pre-treated with PGPR strains B. circulans and B. cereus for 72h showed no signs of soft rot and remained healthy when in vitro contaminated with phytopathogens (Neisseria cinerea and Pichia anomala). Additionally, the PGPR-Bacillus strains were shown to be effective in mitigating the symptoms of soft rot in tomatoes, zucchini, and oranges using in vivo curative treatment. It is true that the majority of pectinolytic phytopathogenic strains exhibited antibiotic resistance. In vivo tests revealed that PGPR-Bacillus cell culture was effective against plant pathogens. Thus, PGPR-Bacillus can be considered a potential biocontrol agent for pectinolytic plant pathogens.

Liver Transplantation for Intrahepatic Cholangiocarcinoma After Chemotherapy and Radioembolization: An Intention-To-Treat Study

Liver transplantation (LT) is a potentially curative experimental treatment for unresectable intrahepatic cholangiocarcinoma (iCC). Pre-transplant downstaging may help defining tumor aggressiveness and drive patient selection. We report the preliminary results of LT for liver-limited unresectable iCC after sequential downstaging with systemic chemotherapy and radioembolization (SYS-TARE). In case of sustained disease stability after SYS-TARE, patients underwent surgical nodal sampling and, if negative, were listed for LT. In this study, 13 patients with unresectable iCC underwent downstaging with SYS-TARE. The median age was 70 years and 77% were female. All had single bulky lesions at diagnosis. After SYS-TARE, 9 (69%) dropped out: 3 due to progressive disease after TARE with no response to second-line, 4 due to extrahepatic disease development and 2 due to positive nodal disease at pre-listing abdominal exploration. The median OS after dropout was 11.5 months. Four (31%) were successfully listed and transplanted. At pathology, viable tumor ranged from 30% to less than 5%. All four patients are alive and disease-free at 73, 40, 12, and 8 months from LT. LT for unresectable iCC after downstaging with SYS-TARE appears to select suitable patients for LT, achieving optimal oncological outcomes in case of response to therapy and no lymphnodal spread.