Objective: This study aims to develop a mechanistically grounded mathematical framework to quantify the time- and dose-dependent inhibitory effects of Pinus massoniana bark extract (PMBE) on BEL-7402 human hepatoma cells, advancing beyond phenomenological approaches through integration of stochastic processes and pharmacodynamic modeling. Methods: A continuous-time branching–Hill hybrid model was constructed by integrating stochastic branching-process kinetics, logistic growth constraints, and sigmoidal pharmacodynamic inhibition (Hill function). The model was calibrated using 48-hour MTT assay data across five PMBE concentrations (20–200 µg/mL) and validated against experimental inhibition rates. Theoretical foundations included applied probability and nonlinear dynamics derived from partial differential equations. Results: The model demonstrated high predictive accuracy, with a maximal inhibition rate of 0.24 at 160 µg/mL PMBE, closely matching empirical observations (0.237 ± 0.015). Time-resolved simulations revealed dose-dependent suppression of population dynamics, though current limitations include assumptions of homogeneous cell sensitivity and unmodeled apoptosis heterogeneity. Conclusion: This hybrid framework bridges stochastic cell behavior with pharmacological inhibition kinetics, providing a quantitative basis for adaptive therapy optimization in hepatocellular carcinoma. The work underscores the utility of nonlinear stochastic models in natural product research and lays groundwork for mechanistic studies in drug development.
Stereotactic radiosurgery is an effective and safe method that can help prevent the development of deep-seated or large-sized cavernomas. However, there are limited studies on familial, multiple and symptomatic cerebral cavernous malformations (CCM). The approach in these cases is not yet clear. This case is a CCM that can be confused with other brain masses and metastases, and contributes to the literature in terms of genetic transmission, management and treatment of cavernomas.
Rethinking Cancer: A New Paradigm for the Postgenomics Era is a groundbreaking book edited by leading scientists Bernhard Strauss, Marta Bertolaso, Ingemar Ernberg, and Mina J. Bissell, and published by MIT Press in April 27, 2021.
Background: C-Reactive Protein (CRP) is associated with cancer development, survival, and tumor recurrence. A barrier to its use is the inability to interpret changes in CRP levels. Aims: The aim of this study was to determine when a change in CRP is clinically meaningful. Methods: This was a retrospective cohort study of consecutive cancer patients. Those with a solid tumor diagnosis and at least two consecutive CRP measurements postdiagnosis were included. Subjects were divided into Baseline High CRP (bHCRP; CRP ≥ 10 mg/L) and Baseline Normal CRP groups (bNCRP; CRP < 10 mg/L), We identified appropriate CRP cut-off points for CRP levels changes; compared bHCRP and bNCRP; constructed Kaplan- Meier survival plots and Cox Proportional Hazard Model to confirm cut-off points in each group. Results: 1473 were eligible. In bHCRP group, Overall survival (OS) Mean (Standard Error) was 87(2) and 81(4) months for ≥ 50% vs < 50% CRP decrease respectively. In bNCRP group, OS was 90(3) and 105(3) months for ≥ 2x vs < 2x increase in CRP levels, respectively. These differences remained significant after adjusting for confounders. Conclusion: After a baseline normal CRP an increase of 2-fold or greater was associated with clinical and statistically significantly shorter OS. Conversely, after a baseline high CRP a 50% or greater decrease from baseline was associated with longer OS. Quantification of clinically meaningful CRP change could impact more effective CRP use as a biomarker, prognostic indicator and aid therapeutic decision making. This is especially important to reduce healthcare disparities in financially struggling healthcare systems.
Non-small cell lung cancer (NSCLC) is the most common cancer, causing death and disability. Targeted therapy and immunotherapy have had an increasing role in the management of patients with advanced NSCLC. These treatments can produce an excellent curative effect, but the side effects should not be ignored. Skin toxicities such as papulopustular eruption, severe desquamation, and paronychia have a high incidence, seriously affecting patients’ quality of life and even interrupting treatment. Early recognition and adequate management are critical to prevent exacerbation of the lesions. This review describes the common skin toxicities related to targeted therapy and immunotherapy for NSCLC, summarizes the updated research progress of the mechanism, and proposes appropriate treatment and counseling for optimized management.
Objective: Helicobacter pylori is a major cause of gastric cancer. This study aimed to determine the frequency of clarithromycin resistance and its association with point mutations in the 23S rRNA gene. Methods: This study was conducted on 100 patients with gastric disorders who were referred to Valiasr Hospital in 2022. Two biopsy samples were obtained from each patient for pathological and microbiological examinations. Antimicrobial susceptibility testing was performed using the agar dilution method, and polymerase chain reaction (PCR) was used for molecular analysis.Results: Among the patients, 53% (53/100) were diagnosed as H. pylori-positive. Pathological findings indicated that 54.7% (29/53) of the H. pylori-positive patients had chronic gastritis, 37.7% (20/53) had severe active gastritis, and 7.5% (4/53) had intestinal metaplasia. Clarithromycin resistance was detected in 13.2% (7/53) of the patients. The MIC50 and MIC90 values were determined to be 0.125 mg/L and 2 mg/L, respectively. PCR results revealed that the A2142G point mutation in the 23S rRNA gene was present in all clarithromycin-resistant strains. Conclusions: Our findings indicate that the presence of the A2142G point mutation in the 23S rRNA gene may be associated with clarithromycin resistance in H. pylori strains. These results underscore the importance of routine screening for resistance genotypes to guide effective treatment strategies.
ABSTRACT Background Accurate pre‐operative clinical staging is essential for guiding treatment in resectable non‐small cell lung cancer (NSCLC). Discrepancies between clinical and pathological staging raise concerns about treatment appropriateness. This study aimed to assess staging accuracy, identify predictors of discordance, and evaluate survival implications. Methods We conducted a retrospective cohort study of Stage I–IIIA NSCLC patients who underwent surgical resection in Melbourne, Australia, between 2011 and 2020. Clinical staging was based on CT, PET, and nodal evaluation; pathological staging was based on surgical histology. The primary outcome was concordance between clinical (cTN) and pathological (pTN) stage. Multivariable logistic and Cox regression models evaluated predictors of discordance and survival. Results Among 221 patients, 58% had concordant clinical and pathological staging. Discordance occurred in 42% of cases—23.9% were upstaged and 17.2% downstaged. N‐stage concordance was associated with female sex, tumor histology, SUV max, and CT‐to‐surgery interval. Nodal discordance independently predicted worse survival (HR 0.43, 95% CI: 0.24–0.77; p = 0.01). Conclusions Substantial discrepancies exist between clinical and pathological staging in resectable NSCLC. Nodal stage discordance is an independent predictor of mortality and highlights the need for improved pre‐operative staging strategies to ensure guideline‐concordant care.
Background: Tumor cells are characterized by a higher production of ribosomes, which are necessary for maintaining enhanced cell growth and subsequent cell division. An increase in ribosome production is associated with aberrant ribosome biogenesis homeostasis, representing specific hallmarks of cancer cells. However, its association with the hepatocellular carcinoma (HCC) microenvironment remains poorly understood. Methods: Using single-sample gene set enrichment analysis (ssGSEA), an RPLscore was constructed to estimate the dysregulation of ribosomal protein large (RPL) genes. The expression of RPL genes and their association with clinical outcomes and the tumor microenvironment (TME) were systematically investigated using bulk-seq and single-cell RNA-seq (scRNA-seq). Results: High expression levels of RPL in HCC were associated with poorer overall survival (OS) (P < 0.001). The RPL score evaluated the RPL gene and verified its independent prognostic value for both OS and relapse-free survival (P = 0.0074 and P < 0.001, respectively). TME analysis indicated that RPL gene dysregulation was closely associated with T cell exhaustion, myeloid-derived suppressor cell (MDSC) infiltration, and vascular dysplasia may be promoted by arginine deficiency (P = 7.6 × 10-10). The scRNA-seq data suggested that the RPL score was positively and significantly associated with the tumor biodiversity score (ITH score). Conclusion: The study highlights the prognostic value of the RPL score and its potential role in mediating immune evasion of HCC, which may provide an impetus for the development of new targets for the treatment of HCC.
Aims: Nanotherapeutics are being explored as a potential solution to treat inflammation-induced cancer. Nanotherapeutics enhance innate immune cells' immunity, enabling them to fight tumors effectively. These cells secrete specific chemicals like cytokines, allowing them to replicate quickly and respond to future threats, making them suitable for immunotherapy.Methods: Nanotechnology can significantly improve human health by enhancing infection detection, prevention, and treatment. Nanomedicines, composed of restorative and imaging compounds in submicrometer-sized materials, aim to deliver effective treatments and limit inflammation in healthy body areas. Combining nanotechnology and clinical sciences, nanoparticles are suitable for gene therapy and have been developed for treating various diseases, including cancer, cardiovascular, diabetes, pulmonary, and inflammatory diseases.Results: Neutrophils and their offspring, including films and extracellular vehicles, are crucial drug transporters for enhanced growth therapy. Tumor microenvironment inputs can modify tumor-associated neutrophils (TANs), which are essential for tumor growth and healing. Human tumor intratumor heterogeneity is crucial for tumor growth and healing. Nanomedicines have shown potential in targeted delivery, toxicity reduction, and therapeutic effectiveness enhancement. However, clinical relevance and efficacy remain inadequate due to a lack of understanding of the interaction between nanomaterials, nanomedicine, and biology. The diverse biological milieu impacts the dynamic bioidentity of nanoformulations, and their interactions can modify therapeutic function or cellular absorption.Conclusion: Nanotechnology holds great promise for improving human health by detecting, preventing, and treating infections. Nanomedicines, a fusion of clinical sciences and nanotechnology, use submicrometer-sized transporter materials for therapy delivery and reducing contamination. Nanoparticles' small size and high surface-to-volume ratio can benefit gene therapy. Research has led to a wide range of nanomedicine products globally.
The advent of Knowledge-Based Planning (KBP) models has introduced a transformative approach to Intensity-Modulated Radiation Therapy (IMRT) treatment planning in breast cancer and lung cancer cases. This paper explores the application of KBP models to these specific cancer types, highlighting their potential to enhance treatment accuracy, efficiency, and patient outcomes. By leveraging historical treatment data and machine learning techniques, KBP-IMRT offers a data-driven framework for optimizing dose distributions, minimizing radiation exposure to healthy tissues, and improving overall treatment plan quality. Through a comprehensive review of the literature and clinical case studies, this paper underscores the advantages of KBP-IMRT, such as streamlined planning processes and improved plan consistency, while acknowledging the challenges associated with model development and implementation. As the field of radiotherapy continues to evolve, KBP models hold the promise of shaping the future of personalized and precise cancer treatment strategies.
Surgical resection is still the most important radical treatment for primary hepatocellular carcinoma (HCC), but at present, the resection rate of newly diagnosed patients with HCC is only 30%. The recurrence rate of newly diagnosed patients suitable for surgical resection within 5 years after surgery is as high as 40%~70%. Low initial resection rate and high postoperative recurrence rate are important reasons restricting the overall treatment effects of HCC in China. Under this background, effectively improving the resection rate of HCC and reducing the postoperative recurrence rate have become the key topics to improve the treatment effects of HCC. Some initially unresectable HCC patients may have access to surgery through conversion therapy. Conversion therapy, which mainly involves the combination of local, systemic, and multiple treatment strategies, offers hope for patients with advanced HCC. But there are still some patients who do not benefit from conversion therapy. So, how to improve the conversion success rate is still one of the challenges that clinicians need to solve.
Despite breakthroughs in screening, identification, and therapy, pancreatic cancer (PC) remains a serious issue in cancer-related mortality. This comprehensive review investigates the long-term and latent effects of chemotherapy in PC, focusing on commonly used medicines such as gemcitabine, docetaxel, irinotecan, nab-paclitaxel, and others. Gemcitabine, a common PC medication, causes a variety of adverse effects, including myelosuppression and weariness. Combination therapy, such as docetaxel and irinotecan, enhance toxicity, resulting in problems such as neutropenia and gastrointestinal difficulties. Significantly, chemotherapy-related complications, such as thrombosis and cardiac difficulties connected to paclitaxel, present serious concerns. Erlotinib, gefitinib, vatalanib, and sunitinib studies show significant side effects. Despite ongoing challenges, determining the causes of the low objective response rate in gemcitabine-refractory patients remains challenging. The study emphasizes the importance of future advances in cancer etiology, arguing for large, straightforward studies examining combination chemotherapies to improve tolerance and minimize chemotherapy-induced sequelae. This overview serves as a thorough guide for physicians, researchers, and policymakers as they navigate the complex terrain of PC chemotherapy, providing significant insights to improve patient care.
Purposes: Breast cancer (BC) is a disease in which the breast cells multiply uncontrolled. Breast cancer is one of the most often diagnosed malignancies in women worldwide. Early identification of breast cancer is critical for limiting the impact on affected people's health conditions. The influence of technology and artificial intelligence approaches (AI) in the health industry is tremendous as technology advances. Deep learning (DL) techniques are used in this study to classify breast lumps. Materials and Methods: The study makes use of two distinct breast ultrasound images (BUSI) with binary and multiclass classification. To assist the models in understanding the data, the datasets are exposed to numerous preprocessing and hyperparameter approaches. With data imbalance being a key difficulty in health analysis, due to the likelihood of not having a condition exceeding that of having the disease, this study applies a cutoff stage to impact the decision threshold in the datasets data augmentation procedures. The capsule neural network (CapsNet), Gabor capsule network (GCN), and convolutional neural network (CNN) are the DL models used to train the various datasets. Results: The findings showed that the CapsNet earned the maximum accuracy value of 93.62% while training the multiclass data, while the GCN achieved the highest model accuracy of 97.08\% when training the binary data. The models were also evaluated using a variety of performance assessment parameters, which yielded consistent results across all datasets. Conclusion: The study provides a non-invasive approach to detect breast cancer; and enables stakeholders, medical practitioners, and health research enthusiasts a fresh view into the analysis of breast cancer detection with DL techniques to make educated judgements.
Introduction: Immune checkpoint inhibitors (ICI) are widely used cancer therapies that harness the immune system to target malignant cells but subsequently can cause serious off-target immune-related Adverse Effects (irAEs). Patients with pre-existing autoimmune disease have historically been excluded from ICI clinical trials due to scientific concerns over increased risk of irAEs and flares of underlying autoimmune disease.Methods: We designed a retrospective, single-center, case-control study at a large, academic medical center to evaluate the incidence and severity of irAEs in patients with pre-existing autoimmunity compared to controls. Controls were matched 2:1 for age, sex, cancer histology, and ICI class. Patients were identified with ICD 9 and 10 codes followed by manual chart extraction. Cases were defined as patients with pre-existing, systemic autoimmunity. The primary outcome was severe irAE (Grade 3 or higher by Common Terminology Criteria for Adverse Events) within 6 months of ICI therapy. Secondary outcomes included response to ICIs, resolution of the irAE, ICI rechallenge success, and survival. Statistical analyses were performed by Chi-square, Fishers exact, Mann-Whitney, and Log-rank tests.Results: Of 3,130 patients treated with ICIs from 2015-2021, 28 cases with pre-existing autoimmune disease were identified and were matched with 56 controls. Pre-existing autoimmune conditions included antiphospholipid syndrome, inflammatory polyarthritis, juvenile rheumatoid arthritis, multiple sclerosis, psoriatic arthritis, rheumatoid arthritis, and type I diabetes. Multiple cancer histologies, including genitourinary, gynecologic, head & neck, hepatobiliary, lung, melanoma, and pancreatic, were represented. Six of 28 cases (21.4%) experienced severe irAEs compared to 9/56 (16.1%) controls; the odds of developing a severe irAE were not significantly different (OR 0.43, 95% CI 0.083-2.33, p = 0.627, ns). Moreover, there were no significant differences in overall survival or tumor response between the two groups. The majority of irAEs resolved without long-term sequelae (66.7% of cases, 55.6% of controls). The majority of patients who were rechallenged with ICIs were successful in continuing therapy (66.7% of cases, 100% of controls).Conclusion: Our study suggests that patients with pre-existing autoimmune disease can be treated with ICI cancer therapies and experience rates of severe irAEs and overall survival that are similar to those of the general population. These data can aid oncologists in discussing risks and benefits of ICIs when treating patients with pre-existing autoimmunity and solid tumors.
Purpose: Evaluate safety and feasibility of simultaneous biliary drainage (BD) and portal vein embolization (PVE) prior to hepatectomy in hilar cholangiocarcinoma (HCCA) patients. Methods: From January 2010 to June 2022, patients with potentially surgically resectable HCCA who underwent preoperative PVE and BD were analyzed. Type of initial BD, time interval between BD and PVE, changes in future liver remnant (FLR), time interval between BD, PVE and resection, and complications were recorded. Patients were divided into 3 groups based on the BD-PVE interval: Group A: simultaneous BD and PVE or within 7 days (d), n = 6; Group B: d ≥ 7 to ≤ 30, n = 7; Group C: d > 30, n = 14). Primary endpoints were post-PVE complications, FLR change, and resection rate. Secondary endpoints were Clavien-Dindo ≥ 3, Grade B/C Post Hepatectomy Liver Failure (PHLF) and 90 days mortality rate. Results: A total of 27 patients (mean age = 64.4 +/- 11.2 years) underwent both BD and PVE prior to hepatectomy. Mean degree of hypertrophy at 4-6 weeks post-PVE was 10.4 +/- 3.7% with no significant difference between the 3 groups (p > 0.05). Resection was 67% in Group A, and 57% and 36% in groups B and C respectively (p < 0.05). Time to surgery was 38.5 +/- 12 days in Group A, and 60 and 147 days in groups B and C respectively (p = 0.002). No major post PVE SIR complication was reported in group A. Overall rate of Grade III/IV Clavien-Dindo complication was 61.5% with no difference among the three groups (50%, 75%, and 60%; groups A, B and C, respectively). Overall PHLF Grade B/C was reported in 46.2% of patients. No patients in Group A demonstrated Grade B/C PHLF. Conclusion: Simultaneous BD and PVE is safe and reduces the time to surgery, which may help contribute to a higher rate of surgical resection.
Purpose: Breast cancer is a heterogeneous disease, and understanding its characteristics is crucial for effective treatment. Therefore, this study aims to investigate breast carcinomas as a function of hormone receptors (estrogen and progesterone) in the Democratic Republic of the Congo (DRC), which can contribute to better management of breast cancer cases in the country.Methods: We conducted an analytical cross-sectional study from 2014 to 2016 in the cities of Kinshasa and Lubumbashi. Using non-random sampling, we collected 86 cases of breast carcinoma.Results: The study found that out of the 86 cases of breast carcinoma, 33 patients (38.3%) had both types of hormone receptors (ER+/PgR+), while 37 patients (43.0%) had negative results for both receptor types (ER-/PgR-). Additionally, 15 patients (17.4%) had only estrogen receptors. The study did not find any significant association between the presence of estrogen receptors and patient age, T stage, histological type, and Ki67 proliferation index. However, the study did observe that estrogen receptors were significantly more present in grade I and II tumors (74.4%) than in grade III tumors (40.4%) (Odds ratio=4.3 [1.7-10.8]; p=0.003).Conclusion: The findings of this study demonstrate a high prevalence of hormone receptors in breast cancer cases in the DRC. Additionally, the study revealed a significant association between the presence of estrogen receptors and tumor grade, underlining the relevance of these markers in the characterization and treatment of the disease.
Phospho-H2AX or γ-H2AXis a marker of DNA double-stranded breaks and can therefore be used to monitor DNA repair after, for example, irradiation. In addition, positive staining for phospho-H2AX may indicate genomic instability and telomere dysfunction in tumour cells and tissues. Here, we provide a protocol to perform immunostaining for phospho-H2AX on cells, cryosections and formalinfi xed, paraffi n-embedded tissues. Crucial steps in the protocol and troubleshooting suggestions are indicated. We also provide suggestions on how to combine staining against γ-H2AX with stainings against components of the tumour microenvironment, such as hypoxia and blood vessels.
