Search

This article discusses a JSGS paper published in the Annals of Gastroenterological Surgery. The paper focuses on the clinicopathological analysis of 460 cases of carcinoma of the ampulla of Vater (CAV) and identifies six prognostic factors. The study also explores the therapeutic strategy for CAV and suggests that preoperative chemotherapy may be the most effective treatment for aggressive CAV. The article also includes three other papers on preoperative chemotherapy in gastric cancer, colorectal cancer, and colon cancer, highlighting the potential benefits and challenges of this treatment approach. [Extracted from the article]

Introduction: Retinoblastoma is a malignant tumor with a high cure potential when proper therapy is used. The purpose of this paper is to report the clinical features and outcomes of patients with retinoblastoma who were treated with a combination of local and systemic chemotherapy‐based protocols. Method: We retrospectively studied patients treated with systemic chemotherapy plus local treatment between 2003 and 2015 with a follow‐up ≥2 years. We correlated clinical and pathological characteristics with decimal visual acuity (VA) and death. Results: Among 119 patients, 60% had unilateral disease (UNI), and 52% were male. The median presentation age was 19.5 months, 10% had a positive family history, and the most frequent sign was leukocoria (68.8%). Advanced disease was more frequent in eyes with UNI (98.4%) than in eyes with bilateral retinoblastoma (BIL: 55.3%). Enucleation was performed in 97% of UNI eyes and in 55.8% of BIL eyes. The overall globe salvage was 26.6%, 44.25% of BIL eyes. Bilateral enucleation was required in 5%. High‐risk pathologic features occurred in 50% and 37% of eyes enucleated without and with neoadjuvant chemotherapy, respectively. High‐risk features were related to the presence of goniosynechiae in the pathologic specimen and were more frequent in children younger than 10 months or older than 40 months. Extraocular disease was present in 5% of patients, and the death rate related to metastasis of the tumor was 8%. The final VA was ≥ 0.7 in 72.8% and ≥0.1 in 91% of BIL patients. Conclusions: Treatment of retinoblastoma with conservative systemic‐based chemotherapy was associated with an excellent survival rate (92%). Albeit the low overall globe salvage rate, in BIL patients, approximately half the eyes were conserved, and a satisfactory functional visual result was achieved The evaluated protocol is an important treatment option, especially in developing countries. [ABSTRACT FROM AUTHOR]

Epigenetic regulation of genes through posttranslational regulation of proteins is a well‐explored approach for disease treatment, particularly in cancer chemotherapy. Histone deacetylases have shown significant potential as effective drug targets in therapeutic studies aiming to restore epigenetic normality in oncology. Besides their role in modifying histones, histone deacetylases can also catalyze the deacetylation of various nonhistone proteins and participate in the regulation of multiple biological processes. This paper provides a review of the classification, structure, and functional characteristics of the four classes of human histone deacetylases. The increasing abundance of structural information on HDACs has led to the gradual elucidation of structural differences among subgroups and subtypes. This has provided a reasonable explanation for the selectivity of certain HDAC inhibitors. Currently, the US FDA has approved a total of six HDAC inhibitors for marketing, primarily for the treatment of various hematological tumors and a few solid tumors. These inhibitors all have a common pharmacodynamic moiety consisting of three parts: CAP, ZBG, and Linker. In this paper, the structure–effect relationship of HDAC inhibitors is explored by classifying the six HDAC inhibitors into three main groups: isohydroxamic acids, benzamides, and cyclic peptides, based on the type of inhibitor ZBG. However, there are still many questions that need to be answered in this field. In this paper, the structure‐functional characteristics of HDACs and the structural information of the pharmacophore model and enzyme active region of HDAC is are considered, which can help to understand the inhibition mechanism of the compounds as well as the rational design of HDACs. This paper integrates the structural‐functional characteristics of HDACs as well as the pharmacophore model of HDAC is and the structural information of the enzymatic active region, which not only contributes to the understanding of the inhibition mechanism of the compounds, but also provides a basis for the rational design of HDAC inhibitors. [ABSTRACT FROM AUTHOR]

The combination of chemotherapy and photothermal therapy shows great potential in cancer treatment, and the carbon nanomaterials have been attracted great attention in biomedical technology. However, it is still a great challenge to design stimuli‐responsive nano‐carbon‐based drug release systems with integrated functions. In this paper, rod‐like carbon nanomaterials (RCNs) were prepared by the soft template hydrothermal method with glucose as raw materials, which were proved to have high photothermal efficiency (∼23.7%), as well as good biocompatibility and excellent drug‐loading capacity. After that, RCNs were used to load doxorubicin (DOX) as DOX@RCNs for integrated photothermal/chemotherapy towards cancer, which demonstrated 52.2% higher cancer cell killing efficiency than that of RCNs under near infrared (NIR) irradiation in vitro. The authors' approach provided a novel NIR‐responsive nano platform for combined photothermal/chemotherapy towards cancer, which was considered to be of great potential in anticancer applications. [ABSTRACT FROM AUTHOR]

Han, K., Claret, L., Piao, Y., Hegde, P., Joshi, A., Powell, J., Jin, J. and Bruno, R. (2016), Simulations to predict clinical trial outcome of bevacizumab plus chemotherapy vs. chemotherapy alone in patients with first‐line gastric cancer and elevated plasma VEGF‐A. CPT Pharmacometrics Syst. Pharmacol., 5: 352–358. https://doi.org/10.1002/psp4.12064The first author of this paper, K. Han, should be listed as Kelong Han. [Extracted from the article]

Targeted therapy has the potential to be used in the neoadjuvant setting for odontogenic tumors, reducing the morbidities associated with major surgery. In this regard, the aim of this study was to summarize the current evidence on the different forms of targeted therapy, effectiveness, and drawbacks of this course of treatment. Four databases were searched electronically without regard to publication date or language. Grey literature searches and manual searches were also undertaken. Publications with sufficient clinical data on targeted therapy for odontogenic tumors were required to meet the criteria for eligibility. The analysis of the data was descriptive. A total of 15 papers comprising 17 cases (15 ameloblastomas and 2 ameloblastic carcinomas) were included. Numerous mutations were found, with BRAF V600E being most common. Dabrafenib was the most utilized drug in targeted therapy. Except for one case, the treatment reduced the size of the lesion (16/17 cases), showing promise. Most of the adverse events recorded were mild, such as skin issues, voice changes, abnormal hair texture, dry eyes, and systemic symptoms (e.g., fatigue, joint pain, and nausea). It is possible to reach the conclusion that targeted therapy for ameloblastoma and ameloblastic carcinoma may be a useful treatment strategy, based on the findings of the included studies. [ABSTRACT FROM AUTHOR]

In this paper, we discuss the effect of optimal chemotherapy doses on solid tumor during treatment and cancer recurrence after the end of treatment. First, an optimal control problem is designed. Then, by changing the control range, the objective function, and adding a control to the previous problem, three new optimal control problems are constructed. We pursue two critical ideas for the success of the drug delivery system to the patient: minimizing the normalized global population density of cancer cells during treatment and at the end of treatment and minimizing side effects during treatment. The optimal control problem is considered with two linear and quadratic objective functions. These models are solved by a well‐established numerical method with high accuracy and a low discretization cost. The numerical results have confirmed that reducing the total dose of the cytotoxic drugs during the treatment period leads to a rapid recurrence of cancer shortly after the end of the treatment period. [ABSTRACT FROM AUTHOR]

Hepatic arterial infusion chemotherapy in conjunction with the combination therapy of atezolizumab (T) and bevacizumab (A) is widely used in hepatocellular carcinoma. Some adverse events such as hypertension, weakness and elevated transaminase levels occurred during treatment, while there is currently no reported case about thrombocytopenia with concomitant HLA antibody‐positive PTR. We summarize the critical care nursing experience of a patient with PTR because of HLA antibody positivity during hepatic arterial infusion chemotherapy in conjunction with atezolizumab plus bevacizumab (T + A) regimen. This paper explains the nursing measures for patients with severe thrombocytopenia and proposes nursing measures for situations where conventional treatments are ineffective. Key nursing points include the administration of intravenous immunoglobulin (IVIG) and HLA‐compatible platelets, prevention of complications, psychological care, oral care, and skin management. Through systematic treatment and targeted nursing care, the patient's platelet count rebounded after 9 days, leading to a successful recovery and discharge. Subsequent follow‐up assessments revealed the patient's sustained well‐being. Thrombocytopenia is a potential adverse reaction during the treatment of liver cancer. When platelet transfusion is ineffective, vigilance is necessary for the possibility of HLA positivity, and prompt symptomatic management is warranted. [ABSTRACT FROM AUTHOR]

This article is a response to a letter received regarding a research paper titled "Long‐term effects of chemotherapy and radiation received during early childhood on the developing dentition of pediatric cancer patients." The research paper explores the impact of chemotherapy and radiation on the development of teeth in childhood cancer survivors. The letter raised concerns about the dose of radiation received by the jaw and dentition. The authors of the response address these concerns and provide additional information about the study's methodology and findings. They emphasize the need for more definitive information regarding the dose of radiation and chemotherapy received to understand their effects on dental development. [Extracted from the article]

Immunotherapy using immune checkpoint inhibitors (ICIs) has shown superior efficacy compared with conventional chemotherapy in certain cancer types, establishing immunotherapy as the fourth standard treatment alongside surgical intervention, chemotherapy, and radiotherapy. In cancer immunotherapy employing ICIs, CD8‐positive cytotoxic T lymphocytes are recognized as the primary effector cells. For effective clinical outcomes, it is essential that the targeted cancer cells express HLA class I molecules to present antigenic peptides derived from the tumor. However, cancer cells utilize various mechanisms to downregulate or lose HLA class I molecules from their surface, resulting in evasion from immune surveillance. Correlations between prognosis and the integrity of HLA class I molecules expressed by cancer cells have been consistently found across different types of cancer. This paper provides an overview of the regulatory mechanisms of HLA class I molecules and their role in cancer immunotherapy, with a particular emphasis on the significance of utilizing pathological tissues to evaluate HLA class I molecules expressed in cancer cells. [ABSTRACT FROM AUTHOR]

The oxazaphosphorine cyclophosphamide (CP) is a DNA-alkylating agent commonly used in cancer chemotherapy. This anticancer agent is administered as a prodrug activated by a liver cytochrome P450-catalyzed 4-hydroxylation reaction that yields the active, cytotoxic metabolite. The primary metabolite, 4-hydroxycyclophosphamide, equilibrates with the ring-open aldophosphamide that undergoes ß-elimination to yield the therapeutically active DNA cross-linking phosphoramide mustard and the byproduct acrolein. The present paper presents a DFT investigation of the different metabolic phases and an insight into the mechanism by which CP exerts its cytotoxic action. A detailed computational analysis of the energy profiles describing all the involved transformations and the mechanism of DNA alkylation is given with the aim to contribute to an increase of knowledge that, after more than 60 years of unsuccessful attempts, can lead to the design and development of a new generation of oxazaphosphorines. [ABSTRACT FROM AUTHOR]

Microtubule polymerization inhibitors (MPIs) have long been used as anticancer agents because they inhibit mitosis. Microtubules are thought to play an important role in the migration of tumor cells and the formation of tumor blood vessels, and new MPIs are being developed. Many clinical trials of novel MPIs have been conducted in humans, while some clinical studies in dogs have also been reported. More attempts to apply MPIs not only in humans but also in the veterinary field are expected to be made in the future. Meanwhile, MPIs have a risk of cardiotoxicity. In this paper, we review findings on the pharmacological effects and cardiotoxicity of MPIs, as well as the mechanisms of their cardiotoxicity. Cardiotoxicity of MPIs involves not only the direct effects of MPIs on cardiomyocytes but also their effects on vascular function. For example, hypertension induced by impaired vascular function also contributes to the exacerbation of myocardial damage, and blood pressure control may be useful in reducing cardiotoxicity. By combined administration of MPIs and other anticancer agents, MPI efficacy may be enhanced, thereby potentially allowing to keep MPI dosage low. Measurement of myocardial injury markers in blood and echocardiography may be useful for monitoring cardiotoxicity. In particular, two‐dimensional speckle tracking may have high sensitivity for the early detection of MPI‐induced cardiac dysfunction. The exploration of the potential of new MPIs while understanding their toxicity and how to deal with them will lead to the further development of cancer chemotherapy. Microtubule polymerization inhibitors (MPIs) inhibit tumor cell mitosis, migration, and tumor angiogenesis. Clinical trials in humans and dogs have been conducted. However, MPIs have cardiotoxicity. Monitoring myocardial injury markers and echocardiography, particularly two‐dimensional speckle tracking, is recommended. Non‐clinical studies have reported that blood pressure control or combination with other anticancer drugs reduces cardiotoxicity. The exploration of the potential of new MPIs while understanding their toxicity and how to deal with them will lead to the further development of cancer chemotherapy. [ABSTRACT FROM AUTHOR]

Epithelial ovarian cancer (EOC) is an often‐fatal malignancy marked by the development of resistance to platinum‐based chemotherapy. Thus, accurate prediction of platinum drug efficacy is crucial for strategically selecting postoperative interventions to mitigate the risks associated with suboptimal therapeutic outcomes and adverse effects. Tissue‐derived extracellular vesicles (tsEVs), in contrast to their plasma counterparts, have emerged as a powerful tool for examining distinctive attributes of EOC tissues. In this study, 4D data‐independent acquisition (DIA) proteomic sequencing was performed on tsEVs obtained from 58 platinum‐sensitive and 30 platinum‐resistant patients with EOC. The analysis revealed a notable enrichment of differentially expressed proteins that were predominantly associated with immune‐related pathways. Moreover, pivotal immune‐related proteins (IRPs) were identified by LASSO regression. These factors, combined with clinical parameters selected through univariate logistic regression, were used for the construction of a model employing multivariate logistic regression. This model integrated three tsEV IRPs, CCR1, IGHV_35 and CD72, with one clinical parameter, the presence of postoperative residual lesions. Thus, this model could predict the efficacy of initial platinum‐based chemotherapy in patients with EOC post‐surgery, providing prognostic insights even before the initiation of chemotherapy. [ABSTRACT FROM AUTHOR]

Temporal bone squamous cell carcinoma (TBSCC) is a rare and invasive malignant tumor. The common predisposing factors include a history of local radiotherapy and chronic suppurative otitis media. The current treatment approach for TBSCC primarily involves surgery, followed by adjuvant radiotherapy and chemotherapy, based on T staging and high‐risk factors. Although patients with early‐stage TBSCC have a high survival rate after treatment, the majority of patients are diagnosed in the intermediate to advanced stages, with extensive tumor involvement, posing challenges for surgical intervention. Definitive chemoradiotherapy (CRT) serves as a viable alternative for unresectable tumors. Constraints in administering curative radiation doses, due to the tolerance of surrounding organs, can lead to uncontrolled tumor growth. Although programmed cell death 1 inhibitors have demonstrated efficacy in head and neck squamous cell carcinoma and cutaneous squamous cell carcinoma, their application in TBSCC remains underexplored. Herein, we report a case of a 47‐year‐old man diagnosed with unresectable advanced and localized TBSCC. Following inadequate tumor control with primary chemoradiotherapy, immunotherapy was initiated, resulting in disease remission within a follow‐up period of > 4 years. [ABSTRACT FROM AUTHOR]

Background and Aims: Further exploration is needed to recognize symptom clusters and categorize subgroups with distinct cluster patterns and associated risks, focusing on symptoms that are highly self‐reported by patients with breast cancer undergoing chemotherapy. This study aimed to identify subgroups and risk factors for self‐reported high symptom cluster burden among patients with breast cancer undergoing chemotherapy. Methods: A total of 647 participants who met the inclusion criteria were included in the study, with data collected on demographics, disease information, self‐reported symptoms, and psychosocial factors. Latent class analysis was utilized to identify the subgroup, while logistic regression was used to pinpoint predictive risk factors. Results: Latent class analysis revealed three subgroups: the "high burden of all symptoms group" (n = 107, 16.54%), the "high burden of psychological symptoms group" (n = 103, 15.92%), and the "low burden of all symptoms group" (n = 437, 67.54%). Patients in the high burden of all symptom group and high burden of psychological symptom group exhibited significantly worse function outcomes (p < 0.001). Predictive risk factors for the "high burden of all symptom group" included older age, lower self‐efficacy, worse body image, and a higher financial burden. Similarly, patients with high burden of psychological symptom were more likely to have low self‐efficacy, poor body image, and a high financial burden. Conclusion: The study demonstrated the importance of giving more attention to patients with breast cancer who are at risk of developing into membership of high symptom cluster burden group. [ABSTRACT FROM AUTHOR]

Background: Toripalimab, combined with gemcitabine and cisplatin, has been approved as the first‐line treatment for recurrent or metastatic nasopharyngeal carcinoma (RM‐NPC), representing a significant milestone as the first FDA‐approved innovative therapy for this condition. Despite this achievement, there's a lack of data on the cost‐effectiveness of toripalimab for RM‐NPC patients in the American context. Methods: To assess the cost‐effectiveness of toripalimab plus chemotherapy versus chemotherapy alone, a 3‐state partitioned survival model was constructed. The study involved participants with characteristics matching those in the JUPITER‐02 trial. Cost and utility inputs were collected from literature. Main outcomes measured were quality‐adjusted life year (QALY), and incremental cost‐effectiveness ratio (ICER). Univariate and probabilistic sensitivity analyses, subgroup analyses, and scenario analyses were conducted to verify the robustness of results. Results: The study found that the toripalimab regimen resulted in 4.390 QALYs at a cost of $361,813, while the chemotherapy‐only regimen yielded 1.685 QALYs at a cost of $161,632. This translates to an ICER of $74,004/QALY, below the willingness‐to‐pay threshold of $150,000/QALY. Sensitivity analyses indicated that utility values, discount rate, and the price of toripalimab significantly impact INMB. With an 87.10% probability of being cost‐effective at a $150,000/QALY threshold, the probabilistic sensitivity analysis supports toripalimab plus chemotherapy as a viable option. Scenario analysis showed that toripalimab remains cost‐effective unless its price increases by 125%. Additionally, a simulated 15‐year study period increases the ICER to $88,026/QALY. Subgroup analysis revealed ICERs of $76,538/QALY for PD‐L1 positive and $70,158/QALY for PD‐L1 negative groups. Conclusions: Toripalimab in combination with chemotherapy is likely to be a cost‐effective alternative to standard chemotherapy for American patients with RM‐NPC. This evidence can guide clinical and reimbursement decision‐making in treating RM‐NPC patients. [ABSTRACT FROM AUTHOR]

Background: Neoadjuvant chemoimmunotherapy (NCIT) for locally advanced esophageal squamous cell carcinoma (ESCC) is supported by increasing data, but the sample size is limited, and the findings are not completely consistent. We conducted a real‐world study and a meta‐analysis to evaluate the efficacy and safety of NCIT in locally advanced ESCC. Methods: We retrospectively assessed the outcomes of patients with locally advanced ESCC who completed NICT and subsequent esophagectomy at our hospital between January 2019 and December 2022, including pathological complete response (pCR) rate, major pathological response (MPR) rate, 1‐, 2‐, and 3‐year overall survival (OS) rates, disease control rate (DCR), objective response rate (ORR), 1‐year recurrence rate, R0 resection rate and adverse events. Moreover, a meta‐analysis of 27 published literatures was also conducted for comparison. Results: In the analysis, 128 patients were studied, with 25% achieving pCR, 46.1% MPR, and 99.2% R0 resection. The 1‐, 2‐, and 3‐year OS rates were 91.41% (95% CI: 85.15%–95.63%), 75.00% (95% CI: 66.58%–82.23%) and 64.84% (95% CI: 55.91%–73.07%).ORR and DCR were 31.2% (95% CI: 23.31–39.99) and 64.1% (95% CI: 55.15%–72.38%), and the 1‐year recurrence rate was 26.7% (95% CI: 22.5%–38.1%). Treatment‐related events occurred in 96.1% but were acceptable. In a meta‐analysis of 27 studies with 1734 patients, pooled rates for pCR, MPR, ORR, DCR, and R0 resection were 29%, 52%, 71%, 97%, and 98%, respectively, with a 1‐year recurrence rate of 12%. Conclusion: NCIT is safe and provides potential survival benefits for patients with locally advanced ESCC. However, randomized phase 3 trial data is still needed. [ABSTRACT FROM AUTHOR]

Surgical site infections (SSIs) following radical mastectomy in breast cancer patients can significantly affect patient recovery and healthcare resources. Identifying and understanding the risk factors for postoperative wound infections (PWIs) are crucial for improving surgical outcomes. This retrospective study was conducted from June 2020 to June 2023, including 23 breast cancer patients who developed PWIs post‐radical mastectomy and a control group of 46 patients without such infections. Comprehensive patient data, including variables such as intraoperative blood loss, hospital stay duration, body mass index (BMI), operation time, anaemia, drainage time, diabetes mellitus, cancer stage, white blood cell (WBC) count, serum albumin levels and preoperative neoadjuvant chemotherapy, were meticulously gathered. Statistical analyses, including univariate and multivariate logistic regression, were performed using SPSS software (Version 27.0). The univariate analysis identified several factors significantly associated with an increased risk of PWIs, including preoperative neoadjuvant chemotherapy, low serum albumin levels, advanced cancer stage, diabetes mellitus and reduced WBC count. Multivariate logistic regression highlighted anaemia, prolonged drainage time, diabetes mellitus, advanced cancer stage, reduced WBC count, hypoalbuminemia and preoperative neoadjuvant chemotherapy as significant contributors to the increased risk of PWIs. Anaemia, extended drainage time, diabetes mellitus, advanced cancer stage, low WBC count, hypoalbuminemia and preoperative neoadjuvant chemotherapy are key risk factors for SSIs post‐radical mastectomy. Early identification and proactive management of these factors are imperative to reduce the incidence of postoperative infections and enhance recovery outcomes in breast cancer patients. [ABSTRACT FROM AUTHOR]

In this meta‐analysis, we reviewed the findings and definitive findings of a new study that assessed the impact of bevacizumab on wound healing following combined chemotherapy for ovarian cancer (OC). The results of a controlled study that assessed the efficacy of bevacizumab in the treatment of ovarian cancer were retrieved from 4 databases, such as the Web of Science and EMBASE. The results of the adverse event associated with wound healing were determined by comparison of the controlled studies of bevacizumab plus chemotherapy in the treatment of ovarian cancer. A meta‐analysis was conducted with either a randomized or a fixed‐effect model in order to establish an odds ratio for time to event variables and for a binary outcome. In the research literature, 830 trials have been identified and seven have been chosen to be included in a definitive analysis of the trial. Among the 4134 cases who received chemotherapy after operation, 2098 received standard chemotherapy and 2036 received the addition of bevacizumab. A total of 7 trials have shown that the use of bevacizumab in the treatment of ovarian cancer patients has reduced wound healing (OR, 0.55; 95% CI: 0.37, 0.80, p = 0.002). Four trials demonstrated that there was no change in the incidence of haemorrhage in patients with ovarian cancer when administered with or without bevacizumab (OR, 0.48; 95% CI, 0.10, 2.34, p = 0.37). The combined use of bevacizumab and chemotherapy may have a negative effect on the healing of wound. [ABSTRACT FROM AUTHOR]

Background: Cancer patients are increasingly affected by chemotherapy‐related cardiac dysfunction. The reported incidence of this condition vary significantly across different studies. Hypothesis: A better comprehensive understanding of chemotherapy‐related cardiac dysfunction incidence in cancer patients is imperative. Therefore, we performed a meta‐analysis to establish the overall incidence of chemotherapy‐related cardiac dysfunction in cancer patients. Methods: We searched articles in PubMed and EMBASE from database inception to May 1, 2023. Studies that reported the incidence of chemotherapy‐related cardiac dysfunction in cancer patients were included. Results: A total of 53 studies involving 35 651 individuals were finally included in the meta‐analysis. The overall pooled incidence of chemotherapy‐related cardiac dysfunction in cancer patients was 63.21 per 1000 person‐years (95% CI: 57.28−69.14). The chemotherapy‐related cardiac dysfunction incidence increased steeply within half a year of cancer chemotherapy. Also, the trend of chemotherapy‐related cardiac dysfunction incidence appeared to have plateaued after a longer duration of follow‐up. In addition, chemotherapy‐related cardiac dysfunction incidence rates are significantly higher among patients with age ≥50 years versus patients with age <50 years (99.96 vs. 34.48 per 1000 person‐years). The incidence rate of cardiac dysfunction was higher among breast cancer patients (72.97 per 1000 person‐years), leukemia patients (65.21 per 1000 person‐years), and lymphoma patients (55.43 per 1000 person‐years). Conclusion: Our meta‐analysis unveiled a definitive overall incidence rate of chemotherapy‐related cardiac dysfunction in cancer patients. In addition, it was found that the risk of developing this condition escalates within the initial 6 months postchemotherapy, subsequently tapering off to become statistically insignificant after a duration of 6 years. [ABSTRACT FROM AUTHOR]

Resistance to chemotherapy remains a formidable obstacle in acute myeloid leukemia (AML) therapeutic management, necessitating the exploration of optimal strategies to maximize therapeutic benefits. Venetoclax with 3+7 daunorubicin and cytarabine (DAV regimen) in young adult de novo AML patients is evaluated. 90% of treated patients achieved complete remission, underscoring the potential of this regimen as a compelling therapeutic intervention. To elucidate underlying mechanisms governing response to DAV in AML, quantitative phosphoproteomics to discern distinct molecular signatures characterizing a subset of DAV‐sensitive patients is used. Cluster analysis reveals an enrichment of phosphoproteins implicated in chromatin organization and RNA processing within DAV‐susceptible and DA‐resistant AML patients. Furthermore, kinase activity profiling identifies AURKB as a candidate indicator of DAV regimen efficacy in DA‐resistant AML due to AURKB activation. Intriguingly, AML cells overexpressing AURKB exhibit attenuated MCL‐1 expression, rendering them receptive to DAV treatment and maintaining them resistant to DA treatment. Moreover, the dataset delineates a shared kinase, AKT1, associated with DAV response. Notably, AKT1 inhibition augments the antileukemic efficacy of DAV treatment in AML. Overall, this phosphoproteomic study identifies the role of AURKB as a predictive biomarker for DA, but not DAV, resistance and proposes a promising strategy to counteract therapy resistance in AML. [ABSTRACT FROM AUTHOR]

Background: Non‐small cell lung cancer (NSCLC) is often diagnosed at an advanced stage. Clinical trials have demonstrated that first‐line immunotherapy alone or in combination with chemotherapy improves overall survival. However, reports of survival outcomes in real‐world settings are limited. We assessed survival in advanced NSCLC patients treated with immunotherapy alone or in combination with chemotherapy in first‐ or second‐line at the Windsor Regional Cancer Program (WRCP) and compared it to existing literature. Methods: We included patients diagnosed with stage IV NSCLC from January 2015 to December 2020 and treated with first‐line chemoimmunotherapy (ChemoImmuno1), chemotherapy followed by immunotherapy (Chemo1), or immunotherapy followed by chemotherapy (Immno1) in our survival analysis. Patients with oncogene‐addicted mutations were excluded. Results: There were 160 patients of which 41.5% were female. Mean age was 68 years. Median overall survival from time of diagnosis was 474 days (95% CI: 249, 949) with an estimated 5‐year survival of 11.1% (95% CI: 4.5, 21.3). Median OS in ChemoImmuno1 was 9.6 months, in Chemo1 was 19.2 months from time of diagnosis and 10.5 months from time of initiation of immunotherapy, and in Immuno1 was 18.4 months, respectively. Estimated survival at three years from time of diagnosis for ChemoImmuno1 was 17.6% and for Immuno1 was 17.9%. For Chemo1, from diagnosis it was 20.1% and from second‐line therapy it was 15.4%. Survival outcomes were comparable to clinical trials and other studies. Conclusion: Real‐world survival outcomes of immunotherapy for advanced NSCLC are comparable to the existing literature in this single center study. [ABSTRACT FROM AUTHOR]

Background: Mannitol is exclusively recommended in the National Comprehensive Cancer Network guidelines for diuresis in cisplatin (CDDP)‐based chemotherapy. The utility of furosemide, a widely used and convenient diuretic, thus requires clarification. Methods: This is a prospective, single‐centered, open‐label, noninferiority phase II study. Patients with thoracic malignancies who planned to receive CDDP‐based chemotherapy were randomly assigned to receive either mannitol (arm A) or furosemide (arm B). The primary end point was set as the proportion of patients who experienced any grade of "creatinine (Cr) increased" based on the upper limit of the normal range (ULN) during the first cycle as assessed by Common Terminology Criteria for Adverse Events Version 4.0. Secondary end points were Cr increased based on the baseline value during the first cycle, Cr increased after the completion of CDDP, and the proportion of patients with phlebitis. Results: Between April 2018 and March 2022, 115 patients were enrolled and 106 were analyzed. Any grade of Cr increased based on the ULN during the first cycle was 17.3% (arm A) and 24.1% (arm B), respectively (p = 0.34). Therefore, the primary end point was not met. After completion of chemotherapy, any grade of Cr increased was observed in 23.1% (arm A) and 31.5% (arm B), respectively. However, the actual serum Cr level and Cr clearance during the courses were not different between the arms. Phlebitis occurred more frequently in arm A (28.8%) than arm B (16.7%). Conclusions: Mannitol should remain the standard diuresis in CDDP‐based chemotherapy assessed by conventional CTCAE grading, but furosemide can be room for consideration when assessed by actual serum Cr level and Cr clearance. [ABSTRACT FROM AUTHOR]

Chemotherapy is widely used to treat colorectal cancer (CRC). Despite its substantial benefits, the development of drug resistance and adverse effects remain challenging. This study aimed to elucidate a novel role of glucagon in anti‐cancer therapy. In a series of in vitro experiments, glucagon inhibited cell migration and tube formation in both endothelial and tumor cells. In vivo studies demonstrated decreased tumor blood vessels and fewer pseudo‐vessels in mice treated with glucagon. The combination of glucagon and chemotherapy exhibited enhanced tumor inhibition. Mechanistic studies demonstrated that glucagon increased the permeability of blood vessels, leading to a pronounced disruption of vessel morphology. Signaling pathway analysis identified a VEGF/VEGFR‐dependent mechanism whereby glucagon attenuated angiogenesis through its receptor. Clinical data analysis revealed a positive correlation between elevated glucagon expression and chemotherapy response. This is the first study to reveal a role for glucagon in inhibiting angiogenesis and vascular mimicry. Additionally, the delivery of glucagon‐encapsulated PEGylated liposomes to tumor‐bearing mice amplified the inhibition of angiogenesis and vascular mimicry, consequently reinforcing chemotherapy efficacy. Collectively, the findings demonstrate the role of glucagon in inhibiting tumor vessel network and suggest the potential utility of glucagon as a promising predictive marker for patients with CRC receiving chemotherapy. [ABSTRACT FROM AUTHOR]

Patient‐derived cancer organoids (PDOs) hold considerable promise for personalizing therapy selection and improving patient outcomes. However, it is challenging to generate PDOs in sufficient numbers to test therapies in standard culture platforms. This challenge is particularly acute for pancreatic ductal adenocarcinoma (PDAC) where most patients are diagnosed at an advanced stage with non‐resectable tumors and where patient tissue is in the form of needle biopsies. Here the development and characterization of microfluidic devices for testing therapies using a limited amount of tissue or PDOs available from PDAC biopsies is described. It is demonstrated that microfluidic PDOs are phenotypically and genotypically similar to the gold‐standard Matrigel organoids with the advantages of 1) spheroid uniformity, 2) minimal cell number requirement, and 3) not relying on Matrigel. The utility of microfluidic PDOs is proven by testing PDO responses to several chemotherapies, including an inhibitor of glycogen synthase kinase (GSKI). In addition, microfluidic organoid cultures are used to test effectiveness of immunotherapy comprised of NK cells in combination with a novel biologic. In summary, our microfluidic device offers considerable benefits for personalizing oncology based on cancer biopsies and may, in the future, be developed into a companion diagnostic for chemotherapy or immunotherapy treatments. [ABSTRACT FROM AUTHOR]

Background: The need for new therapies to improve survival and outcomes in pediatric oncology along with the lack of approval and accessible clinical trials has led to "out‐of‐trial" use of innovative therapies. We conducted a retrospective analysis of requests for innovative anticancer therapy in Canadian pediatric oncology tertiary centers for patients less than 30 years old between 2013 and 2020. Methods: Innovative therapies were defined as cancer‐directed drugs used (a) off‐label, (b) unlicensed drugs being used outside the context of a clinical trial, or (c) approved drugs with limited evidence in pediatrics. We excluded cytotoxic chemotherapy, cellular products, and cytokines. Results: We retrieved data on 352 innovative therapy drug requests. Underlying diagnosis was primary CNS tumor 31%; extracranial solid tumor 37%, leukemia/lymphoma 22%, LCH 2%, and plexiform neurofibroma 6%. RAS/MAP kinase pathway inhibitors were the most frequently requested innovative therapies in 28% of all requests followed by multi‐targeted tyrosine kinase inhibitors (17%), inhibitors of the PIK3CA‐mTOR‐AKT pathway (8%), immune checkpoints inhibitors (8%), and antibody drug conjugates (8%). In 112 out of 352 requests, innovative therapies were used in combination with another anticancer agent. 48% of requests were motivated by the presence of an actionable molecular target. Compassionate access accounted for 52% of all requests while public insurance was used in 27%. Mechanisms of funding varied between provinces. Conclusion: This real‐world data collection illustrates an increasing use of "out‐of‐trial" innovative therapies in pediatric oncology. This new field of practice warrants further studies to understand the impact on patient trajectory and equity in access to innovative therapies. [ABSTRACT FROM AUTHOR]

Aim: To identify the latent classes of a health‐promoting lifestyle and examine the associations of latent class profile with individual characteristics of breast cancer undergoing chemotherapy in China in order to provide some insights and recommendations for targeted and individualized health education of health‐promoting lifestyle. Design: A descriptive cross‐sectional survey design was used for this work. Methods: A total of 197 patients with breast cancer undergoing chemotherapy recruited from the Breast Cancer Outpatient Chemotherapy Clinic of a Grade 3A hospital were surveyed. Health‐promoting lifestyle was measured using the Health Promotion Lifestyle Profile‐II: Chinese Version Short (HPLP‐IICR). Latent class analysis was used to examine respondents' health‐promoting lifestyle patterns. Associations between the latent class membership and individual characteristics were examined using multinomial logistic regression. Results: Four latent classes were identified: Class 1–Good Nutrition and Poor Physical Activity, Class 2–Poor Health Responsibility and Nutrition, Class 3–Active Health‐Promoting Lifestyle, and Class 4–Medium Spiritual Growth and Poor Other Dimensions. Younger respondents and respondents with a higher score in anxiety and depression were more likely to be classified in Class 4 rather than Class 1 or 3. Respondents with low exercise self‐efficacy were more likely to be classified in Class 4 than the others. Respondents in Class 4 had more chemotherapy symptom severity and interference, and cases of menopause were fewer in Class 4 rather than Class 3. Those in Class 4 were more likely to have been diagnosed with cancer within 3 months than those in Class 1. [ABSTRACT FROM AUTHOR]

Aging is a major risk factor for most chronic disorders, for which cellular senescence is one of the central hallmarks. Senescent cells develop the pro‐inflammatory senescence‐associated secretory phenotype (SASP), which significantly contributes to organismal aging and age‐related disorders. Development of senotherapeutics, an emerging class of therapeutic agents to target senescent cells, allows to effectively delay aging and alleviate chronic pathologies. Here we report preliminary outputs from screening of a natural medicinal agent (NMA) library for senotherapeutic candidates and validated several agents with prominent potential as senomorphics. Rutin, a phytochemical constituent found in a number of plants, showed remarkable capacity in targeting senescent cells by dampening expression of the full spectrum SASP. Further analysis indicated that rutin restrains the acute stress‐associated phenotype (ASAP) by specifically interfering with the interactions of ATM with HIF1α, a master regulator of cellular and systemic homeostasis activated during senescence, and of ATM with TRAF6, part of a key signaling axis supporting the ASAP development toward the SASP. Conditioned media produced by senescent stromal cells enhanced the malignant phenotypes of prostate cancer cells, including in vitro proliferation, migration, invasion, and more importantly, chemoresistance, while rutin remarkably downregulated these gain‐of‐functions. Although classic chemotherapy reduced tumor progression, the treatment outcome was substantially improved upon combination of a chemotherapeutic agent with rutin. Our study provides a proof of concept for rutin as an emerging natural senomorphic agent, and presents an effective therapeutic avenue for alleviating age‐related pathologies including cancer. [ABSTRACT FROM AUTHOR]

Background: Continuation of bevacizumab plus second-line chemotherapy has significantly improved overall and progression-free survival in patients with metastatic colorectal cancer (mCRC). However, the cost-effectiveness of such high cost therapy is still uncertain in China; so this analysis was performed to evaluate the cost-effectiveness of these treatment options from the Chinese health care system perspective. Methods: A cost-effectiveness analysis was conducted using data from the ML18147 trial (ClinicalTrials.gov identifier NCT00700102) by modeling a partitioned survival model. Main evaluation indicators were quality-adjusted life years (QALYs) and incremental cost-effectiveness ratio (ICER) with a willingness to pay (WTP) threshold of $38,201 per QALY. One-way and probabilistic sensitivity analyses were conducted to assess the robustness and stability of the model. Subgroup and scenario analyses were also performed to make our study more relevant. Results: Bevacizumab plus chemotherapy increased 0.12 QALYs and an incremental cost of $22,761.62 compared with chemotherapy, resulting in an ICER of $188,904.09 per QALY. The model was most sensitive to the utility of progression-free survival and the cost of bevacizumab. Compared with chemotherapy, bevacizumab plus chemotherapy had a 0% cost-effectiveness probability, and no cost-effectiveness in subgroups at the WTP threshold of $38,201 per QALY. The scenario analysis found that bevacizumab biosimilar gained an ICER of $126,397.38 per QALY when assuming the cost of drugs was calculated at the most affordable price. Conclusions: At the WTP threshold of $38,201 per QALY, continuation of bevacizumab plus chemotherapy is unlikely considered cost-effective for patients after first progression of mCRC. [ABSTRACT FROM AUTHOR]