Cancer Research Articles

Bidirectional relationship between pancreatic cancer and diabetes mellitus: a comprehensive literature review

Pancreatic cancer (PC) is a fatal malignant disease. It is well known that the relationship between PC and type 2 diabetes mellitus (T2DM) is a complicated bidirectional relationship. The most important factors causing increased risks of pancreatic cancer are hyperglycemia, hyperinsulinemia, pancreatitis, and dyslipidemia. Genetics and the immune system also play an important role in the relationship between diabetes mellitus and pancreatic cancer. The primary contributors to this association involve insulin resistance and inflammatory processes within the tumor microenvironment. The combination of diabetes and obesity can contribute to PC by inducing hyperinsulinemia and influencing leptin and adiponectin levels. Given the heightened incidence of pancreatic cancer in diabetes patients compared to the general population, early screening for pancreatic cancer is recommended. Diabetes negatively impacts the survival of pancreatic cancer patients. Among patients receiving chemotherapy, it reduced their survival. The implementation of a healthy lifestyle, including weight management, serves as an initial preventive measure to mitigate the risk of disease development. The role of antidiabetic drugs on survival is controversial, however, metformin may have a positive impact, especially in the early stages of cancer, while insulin therapy increases the risk of PC.

Chemotherapy activates inflammasomes to cause inflammation-associated bone loss.

Chemotherapy is a widely used treatment for a variety of solid and hematological malignancies. Despite its success in improving the survival rate of cancer patients, chemotherapy causes significant toxicity to multiple organs, including the skeleton, but the underlying mechanisms have yet to be elucidated. Using tumor-free mouse models, which are commonly used to assess direct off-target effects of anti-neoplastic therapies, we found that doxorubicin caused massive bone loss in wild-type mice, a phenotype associated with increased number of osteoclasts, leukopenia, elevated serum levels of danger-associated molecular patterns (DAMPs; e.g. cell-free DNA and ATP) and cytokines (e.g. IL-1β and IL-18). Accordingly, doxorubicin activated the absent in melanoma (AIM2) and NLR family pyrin domain containing 3 (NLRP3) inflammasomes in macrophages and neutrophils, causing inflammatory cell death pyroptosis and NETosis, which correlated with its leukopenic effects. Moreover, the effects of this chemotherapeutic agent on cytokine secretion, cell demise, and bone loss were attenuated to various extent in conditions of AIM2 and/or NLRP3 insufficiency. Thus, we found that inflammasomes are key players in bone loss caused by doxorubicin, a finding that may inspire the development of a tailored adjuvant therapy that preserves the quality of this tissue in patients treated with this class of drugs.

DSCAM-AS1 promotes the development of prostate cancer

PurposeThe purpose of this study was to investigate the role of lncRNA DSCAM-AS1 in prostate cancer to find new therapeutic targets and promote the research progress of prostate cancer.MethodsRT-qPCR was used to detect DSCAM-AS1 expression in prostate cancer tissues, normal tissues, human normal prostate epithelial cells (RWPE), and four prostate cancer cell lines. The clinical and prognostic role of DSCAM-AS1 was evaluated by the Kaplan–Meier curve and chi-square test. Secondly, a dual luciferase reporter gene assay was used to study the regulatory mechanism between miR-338-3p and DSCAM-AS1. Finally, the roles of DSCAM-AS1 and miR-338-3p in prostate cancer cell proliferation and metastasis were explored by CCK-8 and Transwell assays.ResultsIt was found that DSCAM-AS1 upregulation could serve as a warning of deterioration and poor prognosis in prostate cancer patients, and that knockdown of DSCAM-AS1 expression inhibited the progression of prostate cancer cells. In addition, miR-338-3p, a target of DSCAM-AS1, was found to be down-regulated in prostate cancer cells and miR-338-3p knockdown could reverse the inhibitory effect of DSCAM-AS1 silencing on prostate cancer.ConclusionDSCAM-AS1 is up-regulated in prostate cancer and regulates the progression of prostate cancer cells by targeting miR-338-3p.

Social capital in the management of breast cancer in Lagos, Nigeria.

Breast cancer is the most common cancer in women worldwide, necessitating substantial social support during diagnosis and treatment. This study examines the role of social capital in breast cancer management, focusing on the experiences of patients. The objective of the study was to explore the role of social capital in breast cancer management among women living with breast cancer in Lagos, Nigeria. Using a qualitative design, the study recruited 23 women with breast cancer receiving treatment at a teaching hospital in Lagos, Nigeria. Data were content analyzed to identify themes related to social capital. The study found that social capital, crucial for breast cancer patients' emotional and instrumental support, stems from various sources such as relatives, immediate family, spouses, places of worship, friends, and neighbors. Effective coping and management of the condition were facilitated through this support network. However, assistance from places of worship, friends, and neighbors was only accessible to those who openly acknowledged their health conditions and had established connections with these social groups. Relationships led to support only when there was a disclosure of the health condition. (1) This finding reinforces the importance of integrating social support mechanisms including family, friends, and community networks into breast cancer management programs. (2) The study identifies diverse sources of social capital, including relatives, family, spouses, places of worship, friends, and neighbors, stressing the need for tailored support networks. (3) Research reveals the link between health condition disclosure and support accessibility from groups like places of worship and friends, and it emphasizes creating stigma-free environments for patients to disclose health status comfortably. (4) The study highlights family involvement in breast cancer management as crucial for effective coping. Healthcare professionals should prioritize interventions strengthening family support systems. (5) Findings of stress community support for better breast cancer outcomes, advocating for initiatives like support groups and awareness campaigns to boost social capital and aid affected individuals. The study emphasizes the significance of involving family members in the breast cancer management process and highlights the need for support systems within families and communities to facilitate better outcomes for breast cancer patients.

Chemotherapy activates inflammasomes to cause inflammation-associated bone loss

Chemotherapy is a widely used treatment for a variety of solid and hematological malignancies. Despite its success in improving the survival rate of cancer patients, chemotherapy causes significant toxicity to multiple organs, including the skeleton, but the underlying mechanisms have yet to be elucidated. Using tumor-free mouse models, which are commonly used to assess direct off-target effects of anti-neoplastic therapies, we found that doxorubicin caused massive bone loss in wild-type mice, a phenotype associated with increased number of osteoclasts, leukopenia, elevated serum levels of danger-associated molecular patterns (DAMPs; e.g. cell-free DNA and ATP) and cytokines (e.g. IL-1β and IL-18). Accordingly, doxorubicin activated the absent in melanoma (AIM2) and NLR family pyrin domain containing 3 (NLRP3) inflammasomes in macrophages and neutrophils, causing inflammatory cell death pyroptosis and NETosis, which correlated with its leukopenic effects. Moreover, the effects of this chemotherapeutic agent on cytokine secretion, cell demise, and bone loss were attenuated to various extent in conditions of AIM2 and/or NLRP3 insufficiency. Thus, we found that inflammasomes are key players in bone loss caused by doxorubicin, a finding that may inspire the development of a tailored adjuvant therapy that preserves the quality of this tissue in patients treated with this class of drugs.

Long-term quality of life after hybrid robot-assisted and open Ivor Lewis esophagectomy for esophageal cancer in a single center: a comparative analysis

PurposeDue to improved survival of esophageal cancer patients, long-term quality of life (QoL) is increasingly gaining importance. The aim of this study is to compare QoL outcomes between open Ivor Lewis esophagectomy (Open-E) and a hybrid approach including laparotomy and a robot-assisted thoracic phase (hRob-E). Additionally, a standard group of healthy individuals serves as reference.MethodsWith a median follow-up of 36 months after hRob-E (n = 28) and 40 months after Open-E (n = 43), patients’ QoL was assessed using the European Organization for Research and Treatment of Cancer (EORTC) QoL Questionnaire Core 30 (QLQ-C30) and the EORTC Esophagus specific QoL questionnaire 18 (QLQ-OES18).ResultsPatients showed similar clinical-pathological characteristics, but hRob-E patients had significantly higher ASA scores at surgery (p < 0.001). Patients and healthy controls reported similar global health status and emotional and cognitive functions. However, physical functioning of Open-E patients was significantly reduced compared to healthy controls (p = 0.019). Operated patients reported reduced role and social functioning, fatigue, nausea and vomiting, dyspnea, and diarrhea. A trend towards a better pain score after hRob-E compared to Open-E emerged (p = 0.063). Regarding QLQ-OES18, hRob-E- and Open-E-treated patients similarly reported eating problems, reflux, and troubles swallowing saliva.ConclusionsThe global health status is not impaired after esophagectomy. Despite higher ASA scores, QoL of hRob-E patients is similar to that of patients operated with Open-E. Moreover, patients after hRob-E appear to have a better score regarding physical functioning and a better pain profile than patients after Open-E, indicating a benefit of minimally invasive surgery.

Sexual quality of life and body image of breast cancer patients: uncovering the meaning behind the symptoms

Introducción: Los síntomas del cáncer de mama y los efectos secundarios del tratamiento pueden afectar significativamente a diferentes áreas funcionales de las mujeres. Objetivo: examinar la calidad de vida de mujeres con cáncer de mama. Método: la muestra estuvo compuesta por 240 mujeres de entre 30 y 68 años (M=52; DT=8,68). Aproximadamente el 50% se había sometido a una mastectomía, mientras que al 40% se le había realizado una reconstrucción mamaria. Un cuestionario estructurado constaba de datos sociodemográficos, SQOL-F, EORTC QLQ-C30 y EORTC QLQ-BR23. Resultados: Los resultados sugieren que nuestros pacientes con BC tenían una menor calidad de vida y más dificultades financieras que en la mayoría de los otros estudios, lo que implica algunas diferencias culturales o del sistema de salud. No someterse a una mastectomía se asoció con una mejor calidad de vida sexual, salud global y funcionamiento físico. Por el contrario, las mujeres que se sometieron a mastectomía informaron problemas de imagen corporal y funcionamiento sexual, con síntomas mamarios más prominentes. La reconstrucción se relacionó con una menor calidad de vida y ninguna mejora en la imagen corporal. Conclusiones: La calidad de vida sexual se relacionó principalmente con el estado de salud global, el funcionamiento emocional, los efectos secundarios del tratamiento y la imagen corporal. El funcionamiento emocional y los efectos secundarios fueron predictores importantes de la calidad de vida sexual, mientras que el funcionamiento sexual deteriorado se asoció con una imagen corporal distorsionada. Estos hallazgos pueden servir como guía para formular intervenciones destinadas a mejorar la calidad de vida.

Metal-Graphene Hybrid Terahertz Metasurfaces for Circulating Tumor DNA Detection Based on Dual Signal Amplification.

Terahertz (THz) spectroscopy has impressive capability for label-free biosensing, but its utility in clinical laboratories is rarely reported due to often unsatisfactory detection performances. Here, we fabricated metal-graphene hybrid THz metasurfaces (MSs) for the sensitive and enzyme-free detection of circulating tumor DNA (ctDNA) in pancreatic cancer plasma samples. The feasibility and mechanism of the enhanced effects of a graphene bridge across the MS and amplified by gold nanoparticles (AuNPs) were investigated experimentally and theoretically. The AuNPs serve to boost charge injection in the graphene film and result in producing a remarkable change in the graded transmissivity index to THz radiation of the MS resonators. Assay design utilizes this feature and a cascade hybridization chain reaction initiated on magnetic beads in the presence of target ctDNA to achieve dual signal amplification (chemical and optical). In addition to demonstrating subfemtomolar detection sensitivity and single-nucleotide mismatch selectivity, the proposed method showed remarkable capability to discriminate between pancreatic cancer patients and healthy individuals by recognizing and quantifying targeted ctDNAs. The introduction of graphene to the metasurface produces an improved sensitivity of 2 orders of magnitude for ctDNA detection. This is the first study to report the combined application of graphene and AuNPs in biosensing by THz spectroscopic resonators and provides a combined identification scheme to detect and discriminate different biological analytes, including nucleic acids, proteins, and various biomarkers.

Advances in preclinical assessment of therapeutic targets for bladder cancer precision medicine.

Bladder cancer incidence is on the rise, and until recently, there has been little to no change in treatment regimens over the last 40 years. Hence, it is imperative to work on strategies and approaches to untangle the complexity of intra and inter-tumour heterogeneity of bladder cancer with the aim of improving patient-specific care and treatment outcomes. The focus of this review is therefore to highlight novel targets, advances, and therapy approaches for bladder cancer patients. The success of combining an antibody-drug conjugate (ADC) with immunotherapy has been recently hailed as a game changer in treating bladder cancer patients. Hence, interest in other ADCs as a treatment option is also rife. Furthermore, strategies to overcome chemoresistance to standard therapy have been described recently. In addition, other studies showed that targeting genomic alterations (e.g. mutations in FGFR3, DNA damage repair genes and loss of the Y chromosome) could also be helpful as prognostic and treatment stratification biomarkers. The use of single-cell RNA sequencing approaches has allowed better characterisation of the tumour microenvironment and subsequent identification of novel targets. Personalized functional precision medicine could be another avenue to improve and guide personalized treatment options. Several novel preclinical targets and treatment options have been described recently. The validation of these advances will lead to the development and implementation of robust personalized treatment regimens for bladder cancer patients.

Mindful Night-to-Day: A Pilot Feasibility Trial of a Mindfulness-Based Insomnia and Symptom Management Intervention for Patients with Hematologic Cancer

ABSTRACT Objectives Patients with hematologic cancer experience severe symptoms (i.e. insomnia, fatigue, pain, distress). Few interventions addressing insomnia and other symptoms exist for this population. Mindfulness-Based Therapy for Insomnia (MBTI) may be appropriate but has only been tested in healthy outpatients. This study aimed to develop and test an adapted MBTI protocol for hematologic cancer patients. Methods Patient (n = 3) and clinician (n = 1) focus groups, and user-testing (N = 5) informed adaptation of Mindful Night-to-Day (MBTI+). A single-arm pilot trial (N = 32) evaluated feasibility (accrual, attrition, adherence), acceptability (intervention satisfaction), and changes to insomnia symptom severity (Insomnia Severity Index; primary outcome) and secondary outcomes (fatigue, pain, distress, pre-sleep arousal, mindfulness, symptom management self-efficacy) at baseline, post-intervention, and 1-month post-intervention. Descriptive statistics and paired sample t-tests were conducted. Results Qualitative feedback informed MBTI+ content, format, and delivery. Mindfulness was used to increase symptom awareness (sleepiness vs. fatigue). Meditations and behavioral skills were applied to inpatient treatment. MBTI+ met feasibility (N = 32/12 months; 8.1% attrition; 83.8% adherence) and acceptability (M = 3.52/4.00) benchmarks. Insomnia symptom severity decreased (d = 1.20) from baseline to post-intervention, as did most secondary outcomes. Conclusions MBTI+ was feasible, acceptable, and showed promise for benefits throughout inpatient and outpatient treatment. Findings warrant further evaluation in a randomized trial.

Anatomical assessment of local recurrence site in breast cancer patients after breast reconstruction and post-mastectomy radiotherapy: implications for radiation volumes and techniques.

Post-mastectomy radiotherapy (PMRT) improves local control rates and survival in patients with adverse prognostic features. The dose coverage to target volumes is critical to yield maximum benefit to treated patients, increasing local control and reducing risk of toxicity. This study aims to assess patterns of breast cancer relapse in patients treated with mastectomy, breast reconstruction and PMRT. Breast cancer patients treated with PMRT between 1992 and 2017 were retrospectively reviewed. Clinical and pathological characteristics of patients were collected. Recurrences were defined as "in field," "marginal" or "out of field." Survival analyses were performed in relation to progression-free survival (PFS) and overall survival (OS). Correlation between baseline features was explored. Data of 140 patients are collected. After a median follow-up time of 72 months, median PFS and OS of 63 and 74 months were detected, respectively. Neoadjuvant chemotherapy, lympho-vascular space invasion (LVI) and size of primary tumor were all significantly associated with worst PFS and OS. Ten patients developed local recurrence: 30% "in field," 30% marginal recurrences, 20% "out of field" and 20% both "in field" and "out of field." No recurrence was detected under the expander, 80% above the device and 20% patients relapsed on IMN chain. The mean distant relapse-free survival was 39 months. Overall, 39 of 140 patients developed distant metastases. The onset of local-regional relapses occurred mainly above the expander/prosthesis, underlying the importance of inclusion of the subcutaneous tissues within the target volume. In order to refine new contouring recommendations for PMRT and breast reconstruction, future prospective studies are needed.

Coping mechanisms employed by caregiver of cancer patients seeking treatment at a tertiary care centre in Northern India

Increasing physical activity among older adults with gynecologic cancers: a qualitative study.

The purpose of this study was to gain an understanding of older gynecologic cancer patients' preferences and opinions related to physical activity during chemotherapy, including interventions to promote physical activity. Gynecologic cancer patients 60years or older receiving chemotherapy at a single institution within the last 12months completed questionnaires and a semi-structured interview asking about their preferences for physical activity interventions aimed at promoting physical activity while receiving treatment. Among the 30 gynecologic cancer patients surveyed and interviewed, a majority agreed with the potential usefulness of a physical activity intervention during chemotherapy (67%) and most reported they would be willing to use an activity tracker during chemotherapy (73%). They expressed a preference for an aerobic activity intervention such as walking, indicated a desire for education from their clinical team on the effects physical activity can have on treatment symptoms, and stated a need for an intervention that could be accessed from anywhere and anytime. Additionally, they emphasized a need for an intervention that considered their treatment symptoms as these were a significant barrier to physical activity while on chemotherapy. In this study of older gynecologic cancer patients receiving chemotherapy, most were open to participating in a virtually accessible and symptom-tailored physical activity intervention to promote physical activity during chemotherapy.

ESCO2’s oncogenic role in human tumors: a pan-cancer analysis and experimental validation

PurposeEstablishment of sister chromatid cohesion N-acetyltransferase 2 (ESCO2) is involved in the mitotic S-phase adhesins acetylation and is responsible for bridging two sister chromatids. However, present ESCO2 cancer research is limited to a few cancers. No systematic pan-cancer analysis has been conducted to investigate its role in diagnosis, prognosis, and effector function.MethodsWe thoroughly examined the ESCO2 carcinogenesis in pan-cancer by combining public databases such as The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression Project (GTEx), UALCAN and Tumor Immune Single-cell Hub (TISCH). The analysis includes differential expression analysis, survival analysis, cellular effector function, gene mutation, single cell analysis, and tumor immune cell infiltration. Furthermore, we confirmed ESCO2’s impacts on clear cell renal cell carcinoma (ccRCC) cells’ proliferative and invasive capacities in vitro.ResultsIn our study, 30 of 33 cancer types exhibited considerably greater levels of ESCO2 expression in tumor tissue using TCGA and GTEx databases, whereas acute myeloid leukemia (LAML) exhibited significantly lower levels. Kaplan-Meier survival analyses in adrenocortical carcinoma (ACC), kidney chromophobe (KICH), kidney renal clear cell carcinoma (KIRC), kidney renal papillary cell carcinoma (KIRP), brain lower grade glioma (LGG), liver hepatocellular carcinoma (LIHC), lung adenocarcinoma (LUAD), mesothelioma (MESO), and pancreatic adenocarcinoma (PAAD) demonstrated that tumor patients with high ESCO2 expression have short survival periods. However, in thymoma (THYM), colon adenocarcinoma (COAD) and rectum adenocarcinoma (READ), ESCO2 was a favorable prognostic factor. Moreover, ESCO2 expression positively correlates with tumor stage and tumor size in several cancers, including LIHC, KIRC, KIRP and LUAD. Function analysis revealed that ESCO2 participates in mitosis, cell cycle, DNA damage repair, and other processes. CDK1 was identified as a downstream gene regulated by ESCO2. Furthermore, ESCO2 might also be implicated in immune cell infiltration. Finally, ESCO2’S knockdown significantly inhibited the A498 and T24 cells’ proliferation, invasion, and migration.ConclusionsIn conclusion, ESCO2 is a possible pan-cancer biomarker and oncogene that can reliably predict the prognosis of cancer patients. ESCO2 was also implicated in the cell cycle and proliferation regulation. In a nutshell, ESCO2 is a therapeutically viable and dependable target.

The suffering is expensive: comparison of therapeutic costs between palliative care and dysthanasia patient

Objectives: Several studies highlight benefits of palliative care for patients with lifethreatening illnesses, especially in terms of pain control and improving life quality. However, there is still research gap, particularly in the Brazilian context, regarding its ability to reduce costs associated with unnecessary invasive tests and procedures often invested in dysthanasia patients, thereby relieving the burden on the healthcare system. Given this scenario, the objective was to determine whether there is a significant difference in healthcare costs between cancer patients receiving palliative care and those in dysthanasia. Method: Documentary research, analyzing 94 medical records of patients who died from cancer in a hospital, divided into two groups: 47 in palliative care and 47 in dysthanasia. The groups had their average costs compared by surveying all tests and procedures recorded in the last 30 days of each patient’s life, with values scored based on the price table of the Unified Health System (Sistema Único de Saúde). Results: Patients receiving curative care in dysthanasia incurred an average cost of 2,316.92 Brazilian Reais (SD = 3,146.60) for tests and procedures in the last 30 days of life. Patients in palliative care had an average cost of 945.40 Brazilian Reais (SD = 2,508.01). There is a statistically significant difference in the invested values between patients in palliative care and those in dysthanasia (U = 620.00; Z = -4.334; p &lt; 0.001). Conclusions: Implementing palliative care can be considered an effective strategy for reducing hospital costs, leading to significant savings within the healthcare system.

Identification of New Pathogenic Variants of Hereditary Diffuse Gastric Cancer.

Hereditary diffuse gastric cancer (HDGC) presents a significant genetic predisposition, notably linked to mutations in the CDH1 and CTNNA1. However, the genetic basis for over half of HDGC cases remains unidentified. The aim of this study is to identify novel pathogenic variants in HDGC and evaluate their protein expression. Among 20 qualifying families, two were selected based on available pedigree and DNA. Whole genome sequencing (WGS) on DNA extracted from blood and whole exome sequencing (WES) on DNA from formalin-fixed paraffin-embedded tissues were performed to find potential pathogenic variants in HDGC. After selection of a candidate variant, functional validation and enrichment analysis were performed. As a result of WGS, three candidate germline mutations (EPHA5, MCOA2, and RHOA) were identified in one family. After literature review and in silico analyses, the RHOA mutation (R129W) was selected as a candidate. This mutation was found in two gastric cancer patients within the family. In functional validation, it showed RhoA overexpression and a higher GTP-bound state in the RhoaR129W mutant. Decreased phosphorylation at Ser127/397 suggested altered YAP1 regulation in the Rho-ROCK pathway. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses linked RhoAR129W overexpression to changed migration/adhesion in MKN1 cell line. However, this RHOA mutation (R129W) was not found in index patients in other families. The RHOA mutation (R129W) emerges as a potential causative gene for HDGC, but only in one family, indicating a need for further studies to understand its role in HDGC pathogenesis fully.

Mapping 18F-FDG Kinetics Together with Patient-Specific Bootstrap Assessment of Uncertainties: An Illustration with Data from a PET/CT Scanner with a Long Axial Field of View.

The purpose of this study was to examine a nonparametric approach to mapping kinetic parameters and their uncertainties with data from the emerging generation of dynamic whole-body PET/CT scanners. Methods: Dynamic PET 18F-FDG data from a set of 24 cancer patients studied on a long-axial-field-of-view PET/CT scanner were considered. Kinetics were mapped using a nonparametric residue mapping (NPRM) technique. Uncertainties were evaluated using an image-based bootstrapping methodology. Kinetics and bootstrap-derived uncertainties are reported for voxels, maximum-intensity projections, and volumes of interest (VOIs) corresponding to several key organs and lesions. Comparisons between NPRM and standard 2-compartment (2C) modeling of VOI kinetics are carefully examined. Results: NPRM-generated kinetic maps were of good quality and well aligned with vascular and metabolic 18F-FDG patterns, reasonable for the range of VOIs considered. On a single 3.2-GHz processor, the specification of the bootstrapping model took 140 min; individual bootstrap replicates required 80 min each. VOI time-course data were much more accurately represented, particularly in the early time course, by NPRM than by 2C modeling constructs, and improvements in fit were statistically highly significant. Although 18F-FDG flux values evaluated by NPRM and 2C modeling were generally similar, significant deviations between vascular blood and distribution volume estimates were found. The bootstrap enables the assessment of quite complex summaries of mapped kinetics. This is illustrated with maximum-intensity maps of kinetics and their uncertainties. Conclusion: NPRM kinetics combined with image-domain bootstrapping is practical with large whole-body dynamic 18F-FDG datasets. The information provided by bootstrapping could support more sophisticated uses of PET biomarkers used in clinical decision-making for the individual patient.

From desert flora to cancer therapy: systematic exploration of multi-pathway mechanisms using network pharmacology and molecular modeling approaches

Ovarian cancer, often labeled a “silent killer,” remains one of the most compelling and challenging areas of cancer research. In 2019 alone, a staggering 222,240 new cases of ovarian cancer were reported, with nearly 14,170 lives tragically lost to this relentless disease. The absence of effective diagnostic methods, increased resistance to chemotherapy, and the heterogeneous nature of ovarian cancer collectively contribute to the unfavorable prognosis observed in the majority of cases. Thus, there is a pressing need to explore therapeutic interventions that offer superior efficacy and safety, thereby enhancing the survival prospects for ovarian cancer patients. Recognizing this potential, our research synergizes bioinformatics with a network pharmacology approach to investigate the underlying molecular interactions of Saudi Arabian flora (Onopordum heteracanthum, Acacia ehrenbergiana, Osteospermum vaillantii, Cyperus rotundus, Carissa carandas, Carissa spinarum, and Camellia sinensis) in ovarian cancer treatment. At first, phytoconstituents of indigenous flora and their associated gene targets, particularly those pertinent to ovarian cancer, were obtained from open-access databases. Later, the shared targets of plants and diseases were compared to identify common targets. A protein–protein interaction (PPI) network of predicted targets was then constructed for the identification of key genes having the highest degree of connectivity among networks. Following that, a compound–target protein–pathway network was constructed, which uncovered that, namely, hispidulin, stigmasterol, ascorbic acid, octopamine, cyperene, kaempferol, pungenin, citric acid, d-tartaric acid, beta-sitosterol, (−)-epicatechin gallate, and (+)-catechin demonstrably influence cell proliferation and growth by impacting the AKT1 and VEGFA proteins. Molecular docking, complemented by a 20-ns molecular dynamic (MD) simulation, was used, and the binding affinity of the compound was further validated. Molecular docking, complemented by a 20-ns MD simulation, confirmed the binding affinity of these compounds. Specifically, for AKT1, ascorbic acid showed a docking score of −11.1227 kcal/mol, interacting with residues Ser A:240, Leu A:239, Arg A:243, Arg C:2, and Glu A:341. For VEGFA, hispidulin exhibited a docking score of −17.3714 kcal/mol, interacting with Asn A:158, Val A:190, Gln B:160, Ser A:179, and Ser B:176. To sum up, both a theoretical and empirical framework were established by this study, directing more comprehensive research and laying out a roadmap for the potential utilization of active compounds in the formulation of anti-cancer treatments.

Reconstructive flap surgery in head and neck cancer patients: an interdisciplinary view of the challenges encountered by radiation oncologists in postoperative radiotherapy

BackgroundMajor advances have been made in reconstructive surgery in the last decades to reduce morbidity in head and neck cancer. Flaps are now present in 80% of patients with oral cavity cancer to cover anatomic, functional, and cosmetic needs. However, gaps in interdisciplinary innovation transfer from surgery to postoperative radiotherapy (poRT) remain challenging. We aimed to provide an interdisciplinary view of the challenges encountered by radiation oncologists in planning head and neck postoperative radiotherapy.MethodsA systematic and critical review was conducted to address areas of optimization in surgery and radiology that may be relevant to poRT.ResultsDespite extensive surgical literature on flap techniques and salvage surgery, 13 retrospective series were identified, where flap outcomes were indirectly compared between surgery alone or poRT. These low-evidence studies suggest that radiotherapy accelerates flap atrophy, fibrosis, and osteoradionecrosis and deteriorates functional outcomes. Preliminary evidence suggests that tumor spread occurs at the flap–tissue junction rather than in the flaps. One prospective 15-patient study showed 31.3% vs. 39.2% flap volume reduction without or with poRT. In an international consensus, experts recognized the needs for optimized flap-sparing poRT against flap-related functional deterioration and bone damage. CT, MRI, and PET-CT modalities show potential for the delineation of the junction area between native tissues and flap for flap segmentation and to characterize flap-specific changes quantitatively and correlate them with patterns of relapse or complications.ConclusionFlap management in poRT is insufficiently documented, but poRT seems to damage flaps. Current gaps in knowledge underscore the need for prospective flap assessment and interdisciplinary trials investigating flap morbidity minimization by flap-sparing poRT planning.

Comparison of the effect of ultrasounic-harmonic scalpel and electrocautery in the treatment of axillary lymph nodes during radical surgery for breast cancer

ObjectiveTo compare the efficacy of ultrasounic-harmonic scalpel and electrocautery in the treatment of axillary lymph nodes during radical surgery for breast cancer.MethodsA prospective study was conducted in the Department of Breast Surgery, Zhongda Hospital Affiliated to Southeast University. A total of 128 patients with pathologically confirmed breast cancer who were treated by the same surgeon from July 2023 to November 2023 were included in the analysis. All breast operations were performed using electrocautery, and surgical instruments for axillary lymph nodes were divided into ultrasounic-harmonic scalpel group and electrocautery group using a random number table. According to the extent of lymph node surgery, it was divided into four groups: sentinel lymph node biopsy, lymph node at station I, lymph node at station I and II, and lymph node dissection at station I, II and III. Under the premise of controlling variables such as BMI, age and neoadjuvant chemotherapy, the effects of ultrasounic-harmonic scalpel and electrocautery in axillary surgery were compared.ResultsCompared with the electrosurgical group, there were no significant differences in lymph node operation time, intraoperative blood loss, postoperative axillary drainage volume, axillary drainage tube indwelling time, postoperative pain score on the day after surgery, and the incidence of postoperative complications (p>0.05).ConclusionThere is no significant difference between ultrasounic-harmonic scalpel and electrocautery in axillary lymph node treatment for breast cancer patients, which can provide a basis for the selection of surgical energy instruments.