Hasil untuk "Neoplasms. Tumors. Oncology. Including cancer and carcinogens"

C. Walko, C. Lindley

Tommaso A. Salamone, Sofia Marotta, Stella Mrmić et al.

Abstract Background Trastuzumab (TZ) resistance remains a significant challenge in the treatment of human epidermal growth factor receptor 2 (HER2)-positive epithelial ovarian cancer (EOC), necessitating novel therapeutic strategies to improve treatment efficacy. Functionalized gold nanoparticles (AuNPs) constitute a promising platform for drug delivery and the ability to enhance tumor targeting via the enhanced permeability and retention (EPR) effect. miR-200c, a well-established tumor suppressor microRNA (miRNA), plays a crucial role in inhibiting epithelial-mesenchymal transition (EMT). However, its role in modulating HER2 signaling pathways and sensitizing ovarian cancer cells to TZ remains largely unexplored. Here, we investigate for the first time the combinatorial effect of miR-200c and thiol-functionalized AuNPs (< 10 nm) loaded with TZ (AuNPs-TZ) in overcoming TZ resistance and enhancing treatment efficacy in ovarian cancer cells. Results Pristine AuNPs were not cytotoxic, confirming their biocompatibility as a nanocarrier for TZ delivery. AuNPs were loaded noncovalently with TZ and maintained colloidal stability to prevent aggregation while facilitating effective cellular uptake. Treatment of ovarian cancer cells overexpressing miR-200c with AuNPs-TZ significantly reduced cell viability and increased apoptosis. Immunoblot analysis showed a reduction of phosphorylated HER2 and downstream Kirsten Rat Sarcoma Virus (KRAS) signaling. Furthermore, transmission electron microscopy (TEM) demonstrated morphological changes in miR-200c-transfected ovarian cancer cells and confirmed the localization of AuNPs carrying TZs on the cell membrane and in the cytoplasm. Conclusions These findings highlight the potential of AuNPs-TZ delivery combined with miR-200c as a promising therapeutic strategy to improve the response of HER2-positive EOC to TZ treatment. These results imply the need to further develop AuNP/miRNA-based combinatorial therapies as a viable nanomedicine approach for drug-resistant cancers. Graphical Abstract

Mohammad Hourani, Selvaraj Giridharan, Fathi Azribi et al.

We report a distinctive case of malignant oncocytic carcinoma originating in the pancreas, an organ rarely associated with such tumours. We discuss the diagnostic journey, highlighting the tumour’s resemblance to renal cell carcinoma but without renal involvement. A significant aspect of this case is the successful and sustained response to combined immunotherapy and tyrosine kinase inhibitors, demonstrating a potential therapeutic pathway for similar rare cases. This study contributes to a deeper understanding of pancreatic oncocytic tumours and their management.

Hua Feng, Shuxian Shang, Kun Chen et al.

BackgroundThere is evidence of a modest reduction in skin cancer risk among metformin users. However, no studies have further examined the effects of metformin on melanoma survival and safety outcomes. This study aimed to quantitatively summarize any influence of metformin on the overall survival (OS) and immune-related adverse effects (irAEs) in melanoma patients.MethodsSelection criteria: The inclusion criteria were designed based on the PICOS principles. Information sources: PubMed, EMBASE, Cochrane Library, and Web of Science were searched for relevant literature published from the inception of these databases until November 2023 using ‘Melanoma’ and ‘Metformin’ as keywords. Survival outcomes were OS, progression-free survival (PFS), recurrence-free survival (RFS), and mortality; the safety outcome was irAEs. Risk of bias and data Synthesis: The Cochrane tool for assessing the risk of bias in randomized trial 2 (RoB2) and methodological index for non-randomized studies (MINORS) were selected to assess the risk of bias. The Cochrane Q and I2 statistics based on Stata 15.1 SE were used to test the heterogeneity among all studies. Funnel plot, Egger regression, and Begg tests were used to evaluate publication bias. The leave-one-out method was selected as the sensitivity analysis tool.ResultsA total of 12 studies were included, involving 111,036 melanoma patients. The pooled HR for OS was 0.64 (95% CI [0.42, 1.00], p = 0.004, I2 = 73.7%), HR for PFS was 0.89 (95% CI [0.70, 1.12], p = 0.163, I2 = 41.4%), HR for RFS was 0.62 (95% CI [0.26, 1.48], p = 0.085, I2 = 66.3%), and HR for mortality was 0.53 (95% CI [0.46, 0.63], p = 0.775, I2 = 0.0%). There was no significant difference in irAEs incidence (OR = 1.01; 95% CI [0.42, 2.41]; p = 0.642) between metformin and no metformin groups.DiscussionThe improvement in overall survival of melanoma patients with metformin may indirectly result from its diverse biological targets and beneficial effects on multiple systemic diseases. While we could not demonstrate a specific improvement in the survival of melanoma patients, the combined benefits and safety of metformin for patients taking the drug are worthy of recognition.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier CRD42024518182.

Ivo Dilber, Stjepko Pleština, Stjepko Pleština et al.

Gastric cancer ranks fourth among the most commonly diagnosed cancers, with over a million new cases diagnosed worldwide each year. Acute and chronic kidney damage are common in patients with malignant diseases and are associated with increased risk of complications and mortality. Rarely, acute renal insufficiency may result from bilateral infiltration of renal parenchyma by tumor cells from another organ. We present a case of a patient with clinical suspected gastric cancer and metastases to the kidneys leading to acute renal failure requiring hemodialysis. Despite gastric biopsies, no tumor cells were found, while histopathological examination of enlarged intra-abdominal lymph node biopsy material confirmed adenocarcinoma of signet ring cell originating from the digestive system. Stomach cancer was identified as the most likely primary site after the kidney biopsy was performed. To the best of our knowledge, no case of gastric cancer leading to kidney metastases and acute renal failure requiring renal replacement therapy was yet described. Multidisciplinary collaboration among oncologists, urologists, radiologists, pathologists, and nephrologists is essential for the optimal treatment outcome of these patients, who generally have a poor prognosis.

Franziska Maria Ippen, Angelika Scherm, Tobias Kessler et al.

Abstract Background Glioblastoma (GB) is the most common malignant primary brain tumor in adults and is associated with a poor prognosis. Current treatment guidelines outline the standard of care for patients with newly diagnosed GB; however, there is currently no well‐established consensus for the treatment of progressive GB. With this systematic meta‐analysis of recently published randomized controlled trials (RCTs), we aim to establish evidence on targeted agents in the treatment of patients with progressive GB. Material and Methods We conducted searches across the Cochrane Library, Pubmed, MEDLINE (Ovid), ClinicalTrials.gov, WHO‘s International Clinical Trials Registry Platform and Google Scholar, encompassing the time span from 1954 to 2022, aiming to identify RCTs evaluating targeted therapies in patients with progressive GB. In order to perform a random‐effects meta‐analysis, we extracted hazard ratios (HRs) of overall survival (OS) and progression‐free survival (PFS). Results We included 16 RCTs (n = 3025 patients) in the systematic meta‐analysis. Formally, regorafenib (RR 0.50; 95% CI 0.33–0.75), Depatux‐M + TMZ (RR 0.66; 95% CI 0.47–0.93) and rindopepimut + bevacizumab (RR 0.53; 95% CI 0.32–0.88) were associated with an improved OS compared to the control arm. The combination of bevacizumab + CCNU (RR = 0.49; 95% CI 0.35–0.69) and regorafenib (RR 0.65; 95% CI 0.44–0.95) were formally associated with improved PFS. Conclusions The aim of this systematic meta‐analysis was to establish evidence for the use of targeted therapies in progressive GB. While some studies demonstrated benefits for OS and/or PFS, those results have to be interpreted with caution as most studies had major methodological weaknesses, including potential differences in sample size, trial design, or the initial distribution of prognostic factors.

Dr. Marcos F. Moraes, Dr. Benedito Barreto de Oliveira

O Dia Nacional de Combate ao Câncer foi instituído pelo Ministério da Saúde, por meio da Portaria n2 707, de 07 de dezembro de 1988, com o objetivo de evocar a importância histórica das entidades de combate ao câncer, de consagrar os serviços que elas têm prestado ao Brasil e de proporcionar a mobilização popular para os aspectos educativos e sociais do combate ao câncer.

Yongzhi Li, Zejin Ou, Danfeng Yu et al.

Abstract Background Over past decades, epidemiological patterns of liver cancer (LC) have changed dramatically. The Global Burden of Disease (GBD) study provides an opportunity for tracking the progress in cancer control with its annual updated reports at national, regional and global level, which can facilitate the health decision-making and the allocation of health resources. Therefore, we aim to estimate the global, regional and national trends of death caused by liver cancer due to specific etiologies and attributable risks from 1990 to 2019. Materials and methods Data was collected from the GBD study 2019. Estimated annual percentage changes (EAPC) were used to quantify the trends of age-standardized death rate (ASDR). We applied a linear regression for the calculation of estimated annual percentage change in ASDR. Results From 1990 to 2019, the ASDR of liver cancer decreased globally (EAPC =  − 2.23, 95% confidence interval [CI]: − 2.61 to − 1.84). Meanwhile, declining trends were observed in both sexes, socio-demographic index (SDI) areas, and geographies, particularly East Asia (EAPC =  − 4.98, 95% CI: − 5.73 to − 4.22). The ASDR for each of the four major etiologies fell globally, while liver cancer caused by hepatitis B had the largest drop (EPAC =  − 3.46, 95% CI: − 4.01 to − 2.89). China has had dramatic decreases in death rates on a national scale, particularly when it comes to the hepatitis B etiology (EAPC =  − 5.17, 95% CI: − 5.96 to − 4.37). However, certain nations, such as Armenia and Uzbekistan, saw a rise in liver cancer mortality. Controlling smoking, alcohol, and drug use contributed to a drop in LC-related mortality in the majority of socio-demographic index areas. Nevertheless, the excessive body mass index (BMI) was portrayed as the underlying cause for LC fatalities. Conclusion From 1990 to 2019, there was a worldwide decrease in deaths caused by liver cancer and its underlying causes. However, rising tendencies have been observed in low-resource regions and countries. The trends in drug use- and high BMI-related death from liver cancer and its underlying etiologies were concerning. The findings indicated that efforts should be increased to prevent liver cancer deaths through improved etiology control and risk management.

Cindy Juliane da Silva Ferreira, I. Caires, Walfrido José Bezerra da Costa Neto et al.

SUMMARY OBJECTIVE: This study aimed to evaluate the expression of C-X-C motif chemokine ligand 12 and its C-X-C chemokine receptor type 4, and the tumor-stroma ratio using collagen stromal content of breast cancer samples, correlating it with clinicopathological data. METHODS: Through a retrospective cohort study, samples were obtained from female patients, over 18 years of age, with the disease in stages 1–4, who underwent mastectomy or lumpectomy. The biopsies were provided by the Oncology sector of the Hospital das Clínicas of Universidade Federal de Pernambuco, Recife city, in 2011–2014, including samples of invasive ductal carcinoma, ductal carcinoma in situ, or benign changes (fibroadenoma and hypertrophy), which were analyzed between 2020 and 2022 by immunohistochemistry for the expression of stromal cell characteristics. Collagen content was tested by Gomori staining and digital analysis of images. RESULTS: Absence of stromal expression of C-X-C motif chemokine ligand 12 was associated with longer disease-free survival (disease-free survival=0.481), and expression of C-X-C chemokine receptor type 4 was associated with lower disease-free survival. An association was observed between clinicopathological variables and stromal expression of chemokines, that is, an association of stromal C-X-C motif chemokine ligand 12 with histological grade, angiolymphatic invasion, and an association between C-X-C chemokine receptor type 4 expression and histological grade. Analyses of digital pixels images of collagen and tumor cells showed a lower percentage of collagen in the invasive ductal carcinoma samples (39%), unlike samples without neoplasms (78%). CONCLUSION: Low expression of C-X-C motif chemokine ligand 12 may be associated with a worse prognosis for breast cancer. Collagen staining analyzed using digital images represents an opportunity for clinical application and is indicative of the prognosis of the tumor microenvironment in breast carcinoma.

T. Guimarães, Karla Menezes Cardoso, C. Marto et al.

Photodynamic therapy (PDT) in small animals’ oncology has been under research focus, pointing to new treatment possibilities. Moreover, several animal studies constitute experimental human disease models due to the similarity of tumor biology between animals and man. PDT uses photosensitizing compounds without toxicity per se. When subjected to a specific wavelength, the photosensitizers are activated, triggering the production of reactive oxygen species (ROS) that lead to cell death. Additionally, antiangiogenic effects and immune stimulation may also be elicited. PDT is minimally invasive, non-toxic, and does not induce carcinogenic or mutagenic side effects. Thus, it is safe for non-neoplastic tissues compared with other neoplasms treatment modalities. This review describes the applications of PDT in the cancer treatment of small animals, particularly dogs and cats, focusing on the respective photosensitizers and treatment protocols used in trials in this therapeutic modality.

Irawan C, Iskandar M, Harahap AS et al.

Cosphiadi Irawan,1 Martha Iskandar,1 Agnes Stephanie Harahap,2 Cleopas Martin Rumende,3 Maria Francisca Ham2 1Hematology and Medical Oncology Division, Internal Medicine Department, Dr. Cipto Mangunkusumo Hospital, Faculty of Medicine, Universitas Indonesia, Jakarta, 10430, Indonesia; 2Anatomical Pathology Department, Dr. Cipto Mangunkusumo Hospital, Faculty of Medicine, Universitas Indonesia, Jakarta, 10430, Indonesia; 3Internal Medicine Department, Dr. Cipto Mangunkusumo Hospital, Faculty of Medicine, Universitas Indonesia, Jakarta, 10430, IndonesiaCorrespondence: Martha Iskandar, Tel +628161924095, Email marthaiskandar@gmail.comBackground: Treatment response in diffuse large B-cell lymphoma (DLBCL) is heterogenous. The Hans algorithm (using 30% cut-offs for CD10, BCL6, and MUM1 protein expression) has been the most favored method to categorize DLBCL into germinal center B-cell (GCB) and non-GCB subtypes in order to predict prognosis. However, the algorithm’s ability to prognosticate is not always consistent.Methods: This retrospective cohort study was conducted on DLBCL patients receiving R-CHOP therapy at Dr. Cipto Mangunkusumo Hospital, Jakarta from 2014 to 2017. We aimed to compare the prognostic value of Hans algorithm as well as the protein levels of CD10, BCL6, MUM1, and Ki67 at different cut-offs. Ninety-two patients were classified based on Hans algorithm and various proteins at different cut-off values were analyzed with regard to event-free survival at 24 months using survival analysis. The cut-off values were then compared using receiver operating characteristic curves.Results: A significant survival difference was observed with MUM1 expression cut-off of 50% or more (log rank p = 0.035). CD10, BCL6, Ki67, and Hans algorithm showed AUCs below or near 0.5 (0.405, 0.436, 0.498, and 0.413, respectively), whereas MUM1 showed an AUC of 0.835, in predicting events within 24 months. MUM-1 cut-off of 70.5% yielded an optimal trade-off for sensitivity and specificity.Conclusion: MUM1 expression of 50% or more can help predict prognosis in DLBCL patients receiving R-CHOP therapy and can be considered as for use as a single marker to predict prognosis.Keywords: DLBCL, RCHOP, MUM1, Hans algorithm, prognosisMeSH Terms: lymphoma, large B-cell, dIffuse, MUM1 nucleosome-binding protein, human, antineoplastic combined chemotherapy protocols/adverse effects, rituximab/therapeutic use, retrospective studies, prognosis

A. N. KULIKOV, N. V. MURAVYEVA, B. S. BELOV

Background. Patients with autoimmune and inflammatory rheumatic diseases (AIRDs) are at high risk of developing COVID-19. Vaccination is an effective method of preventing this disease, which may be unsafe for patients with AIRDs.The aim of the study is to assess the safety of Gam-COVID-Vac in patients with IVRD in real clinical practice.Material and methods. A cross-sectional study was carried out. The main group consisted of patients with AIRDs, the control group consisted of individuals without AIRDs. All participants were interviewed by the research physician using a unified questionnaire, additional information was obtained from medical records.Results. The study included 222 patients with AIRDs (119 with rheumatoid arthritis, 36 with ankylosing spondylitis, 17 with psoriatic arthritis, 17 with Sjögren's disease, 10 with undifferentiated spondyloarthritis, 8 with systemic lupus erythematosus, 4 with metabolic arthritis, 3 with systemic scleroderma, 3 with systemic vasculitis, 2 with polymyalgia rheumatica, 2 with undifferentiated systemic connective tissue disease, 1 with adult Still's disease) and 111 patients without AIRDs. The number of patients with AIRDs who had a combination of local and systemic adverse events (AE) on the introduction of the first component of the vaccine was significantly less than in the control group (22.1 and 44.1%, respectively, P&lt;0.001). Similar differences were also noted after the introduction of the second component (14.0 and 29.7%, respectively, P&lt;0.001). AEs such as pain at the injection site without restriction of movement, weakness, fever, arthralgia/myalgia, headache, and chills were significantly more common in the control group after the introduction of the first component of the vaccine. After complete immunization, AEs were absent in 35.6% of patients with AIRDs and in 21.6% of control group patients (P=0.01). Exacerbations of AIRDs and new autoimmune phenomena were not registered in any cases.Conclusions. According to preliminary data, immunization of patients with AIRDs with the Gam-COVID-Vac combined vector vaccine appears to be quite safe.

Te Zhang, Wenjie Xia, Xuming Song et al.

Abstract Background Lung adenocarcinoma (LUAD) is the leading cause of death worldwide. However, the roles of long noncoding RNAs (lncRNAs) hijacked by super-enhancers (SEs), vital regulatory elements of the epigenome, remain elusive in the progression of LUAD metastasis. Methods SE-associated lncRNA microarrays were used to identify the dysregulated lncRNAs in LUAD. ChIP-seq, Hi-C data analysis, and luciferase reporter assays were utilized to confirm the hijacking of LINC01977 by SE. The functions and mechanisms of LINC01977 in LUAD were explored by a series of in vitro and in vivo assays. Results We found that LINC01977, a cancer-testis lncRNA, was hijacked by SE, which promoted proliferation and invasion both in vitro and in vivo. LINC01977 interacted with SMAD3 to induce its nuclear transport, which facilitated the interaction between SMAD3 and CBP/P300, thereby regulating the downstream target gene ZEB1. Additionally, SMAD3 up-regulated LINC09177 transcription by simultaneously binding the promoter and SE, which was induced by the infiltration of M2-like tumor-associated macrophages (TAM2), subsequently activating the TGF-β/SMAD3 pathway. Moreover, LINC01977 expression was positively correlated with TAM2 infiltration and SMAD3 expression, especially in early-stage LUAD. Higher chromatin accessibility in the SE region of LINC01977 was observed with high expression of TGF-β. Early-stage LUAD patients with high LIN01977 expression had a shorter disease-free survival. Conclusions TAM2 infiltration induced a rich TGF-β microenvironment, activating SMAD3 to bind the promoter and the SE of LINC01977, which up-regulated LINC01977 expression. LINC01977 also promoted malignancy via the canonical TGF-β/SMAD3 pathway. LINC01977 hijacked by SE could be a valuable therapeutic target, especially for the treatment of early-stage LUAD.

Xingxun Bao, Yanan Zhang, Hairong Zhang et al.

β-Sitosterol (SIT), a white powdery organic substance with a molecular formula of C29H50O, is one of the most abundant naturally occurring phytosterols in plants. With a chemical composition similar to that of cholesterol, SIT is applied in various fields such as medicine, agriculture, and chemical industries, owing to its unique biological and physicochemical properties. Modern pharmacological studies have elucidated good anti-tumor therapeutic effect activity of SIT, which mainly manifests as pro-apoptotic, anti-proliferative, anti-metastatic, anti-invasive, and chemosensitizing on tumor cells. In addition, SIT exerts an anti-tumor effect on multiple malignant tumors such as breast, gastric, lung, kidney, pancreatic, prostate, and other cancers. Further, SIT derivatives with structural modifications are promising anti-tumor drugs with significant anti-tumor effects. This review article focuses on recent studies relevant to the anti-tumor effects of SIT and summarizes its anti-tumor mechanism to provide a reference for the clinical treatment of malignant tumors and the development of novel anti-tumor drugs.

K.T. Beer

To describe the rationale and process how SGRT was implemented in our department from the original decision to daily clinical practice.

Cameron Durfee, P. Argyris, Matthew C. Jarvis et al.

Introduction: Advanced DNA sequencing technologies have revealed a substantial endogenous source of mutations in cancers, the human DNA-mutating enzyme APOBEC3B (A3B). This protein changes DNA cytosines into uracils (C-to-U), which can become “immortalized” in the genome as C-to-T or C-to-G mutations depending on how each uracil lesion is processed. However, mice lack analogous carcinogenic A3 enzymes, which makes a definitive cause-and-effect model of A3-induced carcinogenesis difficult to establish. Results: Using C57BL/6 mice, we have generated a novel genetically engineered mouse model (GEMM) expressing the human protein A3B, where it is driven constitutively from the Rosa26 locus in combination with the strong synthetic CAG promoter. Importantly, tumor-free survival data suggest that CAG A3B mice develop tumors at an increased rate compared to wild-type mice. These CAG A3B mice develop predominantly lymphoid neoplasms including B- and T-cell lymphomas and marked splenomegaly, and less frequently lung and liver cancers. Using immunohistochemical and whole-genome sequencing techniques, we have further characterized the tumors arising in these novel GEMMs. The above analyses thus far have revealed that A3B is actively driving tumor formation, as seen by an enrichment of canonical APOBEC-related mutations in these cancers. Conclusion: Overall, the CAG A3B mice are the first GEMMs demonstrating the potential for A3B to drive tumor formation in vivo, with a predilection towards blood malignancies. They will be an invaluable tool for characterizing A3B-driven mutational processes in an organism and testing novel therapeutic strategies against APOBEC-induced cancer initiation and progression. Citation Format: Cameron C. Durfee, Prokopios P. Argyris, Matthew C. Jarvis, Rena Levin-Klein, Emily K. Law, Reuben S. Harris. A genetically engineered mouse model for carcinogenesis by the human enzyme APOBEC3B [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 925.

S. Levi, R. Czerninski, S. Fischman et al.

Simone Mocellin

Keegan Cooke, Jinghui Zhan, Juan Estrada et al.