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Asian Pacific Journal of Cancer... Jun 2024Breast cancer is one of the most widespread tumors among women worldwide, which is difficult to treat due to the presence of chemoresistance and the risk of tumor...
OBJECTIVE
Breast cancer is one of the most widespread tumors among women worldwide, which is difficult to treat due to the presence of chemoresistance and the risk of tumor recurrence and metastasis. There is a pressing necessity to develop efficient treatments to improve response for treatment and increase prolong survival of breast cancer patients. Photodynamic therapy (PDT) has attracted interest for its features as a noninvasive and relatively selective cancer treatment. This method relies on light-activated photosensitizers that, upon absorbing light, generate reactive oxygen species (ROS) with powerful cell-killing outcomes. Nuclear factor kappa B (NF-κB), a transcription factor, plays a key role in cancer development by regulating cell proliferation, differentiation, and survival. Inhibiting NF-κB can sensitize tumor cells to chemotherapeutic agents. Dimethyl fumarate (DMF), an NF-κB inhibitor approved by the FDA for multiple sclerosis treatment, has further shown promise in suppressing breast cancer cell growth in vitro. We hypothesized that combining PDT with Dimethyl fumarate (DMF) could further enhance therapeutic efficacy for both treatment modalities.
METHODS
In the current study, we explored the PDT effect of 1 and 2 mM aminolaevulinic acid (ALA) and low-power He-Ne laser irradiation combined with different concentrations of DMF (2.5, 1.25, or 0.652 µg/ml) against hormone nonresponsive AMJ13 breast cancer cell line that is derived from Iraqi patient.
RESULTS
Our results demonstrated that co-administration with all tested DMF concentrations significantly enhanced the cytotoxicity of PDT antitumor effect. The combination index analysis showed presence of synergism in combining PDT with DMF.
CONCLUSION
This finding suggests that the combination of PDT with DMF could be a promising novel strategy against triple negative breast cancer that could be applied clinically due to the fact that both of these treatments are already clinically approved therapies.
Topics: Humans; Photochemotherapy; NF-kappa B; Photosensitizing Agents; Aminolevulinic Acid; Female; Cell Proliferation; Breast Neoplasms; Dimethyl Fumarate; Apoptosis; Reactive Oxygen Species; Tumor Cells, Cultured; Cell Line, Tumor
PubMed: 38918667
DOI: 10.31557/APJCP.2024.25.6.2051 -
Asian Pacific Journal of Cancer... Jun 2024This study was designed to determine the role of BRAF V600E and TERT mutations in the incidence of neck lymph node (LN) metastasis in patients with papillary thyroid...
OBJECTIVE
This study was designed to determine the role of BRAF V600E and TERT mutations in the incidence of neck lymph node (LN) metastasis in patients with papillary thyroid carcinoma (PTC).
METHODS
This was a cross-sectional study, involving PTC patients at Dr. Cipto Mangunkusumo Hospital, Jakarta. Data were obtained retrospectively based on medical records, except for BRAF V600E and TERT promoter mutations. Tumor tissue specimens of PTC's patients were transferred to the Integrated Laboratory of Faculty of Medicine, Universitas Indonesia. BRAF gene multiplication was performed with KOD One PCR Master Mix (Toyobo KMM-201), while TERT gene multiplication was performed with PCR Master Mix. Data analysis was performed with SPSS version 20. The data were analyzed using univariate and bivariate analysis with the Chi-Square test.
RESULT
42 PTC patients were included in the study; 19 (45%) had BRAF mutation, 20 (48%) had TERT mutation, and 20 (48%) had LN metastases. BRAF V600E mutation was associated with LN metastasis [p<0.001, OR = 25.33 (95% CI 4.92 - 130.34)], while TERT mutation was not. Patients with BRAF+ and TERT- mutations were 18.00 times (95% CI 2.01 - 161.05) more likely to develop LN metastasis than patients with BRAF- and TERT-. Furthermore, the presence of TERT mutation along with BRAF mutation increased the risk to 60.00 (95% CI 4.72 - 763.04) higher than patients with BRAF- and TERT-.
CONCLUSION
BRAF mutation was associated with LN metastasis in PTC patients, but not TERT mutations. However, the presence of TERT mutation in PTC's patients with BRAF mutation increased the risk of LN metastasis.
Topics: Humans; Telomerase; Proto-Oncogene Proteins B-raf; Female; Lymphatic Metastasis; Male; Promoter Regions, Genetic; Thyroid Neoplasms; Cross-Sectional Studies; Mutation; Adult; Middle Aged; Retrospective Studies; Thyroid Cancer, Papillary; Prognosis; Follow-Up Studies; Carcinoma, Papillary; Indonesia; Biomarkers, Tumor
PubMed: 38918666
DOI: 10.31557/APJCP.2024.25.6.2043 -
Asian Pacific Journal of Cancer... Jun 2024Colorectal cancer (CRC) is a major public health problem and one of leading cancer related death all over the world. One of the prognostic parameters that play a role in...
BACKGROUND
Colorectal cancer (CRC) is a major public health problem and one of leading cancer related death all over the world. One of the prognostic parameters that play a role in different types of cancer is HER2. However, the role of HER2 in CRC and its relation with clinicopathological features and survival is conflicting. We hypothesize that HER2 has different patterns of expression in CRC which may affect the prognosis of patients.
MATERIAL & METHODS
We studied sixty specimens of colorectal carcinoma for HER2 immunohistochemistry and gene amplification and correlate it with clinicopathological features and patients` survival.
RESULTS
Our data showed that negative HER2 expression was statistically associated with female gender (P = 0.010) and low & intermediate tumor budding (P = 0.030). There was a statistically significant relation between HER2 IHC and HER2 FISH amplification (P=0.000). Although neither HER2 immunoexpression and FISH amplification showed significant relation with overall survival nor disease free survival, HER2 amplified CRCs tended to have a worse survival compared with negative CRCs (40 months versus 50 months). The presence of male gender, lymphovascular invasion, nodal metastasis and distant metastasis (P = 0.013, 0.006, 0.006 and 0.000 respectively) were significantly statistically associated with poor overall survival. The presence of tumor grade III and high tumor budding (P = 0.035 and 0.007 respectively) were significantly statistically associated with shorter disease free survival.
CONCLUSIONS
Our results showed that HER2 IHC 3+ staining is highly predictive of HER2 gene amplification in colorectal carcinomas. There is a tendency towards poorer prognosis in amplified HER2 CRC cases.
Topics: Humans; Male; Colorectal Neoplasms; Female; Receptor, ErbB-2; Middle Aged; Egypt; Prognosis; Survival Rate; Biomarkers, Tumor; Gene Amplification; Aged; Adult; Follow-Up Studies; In Situ Hybridization, Fluorescence; Lymphatic Metastasis; Neoplasm Staging; Immunohistochemistry
PubMed: 38918664
DOI: 10.31557/APJCP.2024.25.6.2023 -
Asian Spine Journal Jun 2024Retrospective study.
Correlation between the maximum standard uptake value and mean Hounsfield unit on single-photon emission computed tomography-computed tomography to discriminate benign and metastatic lesions among patients with breast cancer.
STUDY DESIGN
Retrospective study.
PURPOSE
To compare and correlate technetium-99m methylene diphosphonate uptake between benign and metastatic bone lesions using semiquantitative analysis of maximum standard uptake value (SUVmax) and mean Hounsfield unit (HU) in single-photon emission computed tomography-computed tomography (SPECT-CT).
OVERVIEW OF LITERATURE
Qualitative interpretation of metastatic bone lesions in breast cancer on bone scintigraphy is often complicated by coexisting benign lesions.
METHODS
In total, 185 lesions were identified on bone and SPECT-CT scans from 32 patients. Lesions were classified as metastatic (109 sclerotic lesions) and benign (76 lesions) morphologically on low-dose CT. Semiquantitative analysis using SUVmax and mean HU was performed on the lesions and compared. To discriminate benign and metastatic lesions, the correlation between SUVmax and mean HU was determined using the intraclass correlation coefficients.
RESULTS
The SUVmax was higher in metastatic lesions (20.66±14.36) but lower in benign lesions (10.18±12.79) (p<0.001). The mean HU was lower in metastatic lesions (166.62±202.02) but higher in benign lesions (517.65±192.8) (p<0.001). A weak negative correlation was found between the SUVmax and the mean HU for benign lesions, and a weak positive correlation was noted between the SUVmax and the mean HU on malignant lesions with no statistical significance (p=0.394 and 0.312, respectively). The cutoff values obtained were 10.8 for SUVmax (82.6% sensitivity and 84.2% specificity) and 240.86 for the mean HU (98.7% sensitivity and 88.1% specificity) in differentiating benign from malignant bone lesions.
CONCLUSIONS
Semiquantitative assessment using SUVmax and HU can complement qualitative analysis. Metastatic lesions had higher SUVmax but lower mean HU than benign lesions, whereas benign lesions demonstrated higher mean HU but lower SUVmax. A weak correlation was found between the SUVmax and the mean HU on malignant and benign lesions. Cutoff values of 10.8 for the SUVmax and 240.86 for the mean HU may differentiate bone metastases from benign lesions.
PubMed: 38917860
DOI: 10.31616/asj.2022.0451 -
JCO Clinical Cancer Informatics Jun 2024The estimation of prognosis and life expectancy is critical in the care of patients with advanced cancer. To aid clinical decision making, we build a prognostic strategy...
PURPOSE
The estimation of prognosis and life expectancy is critical in the care of patients with advanced cancer. To aid clinical decision making, we build a prognostic strategy combining a machine learning (ML) model with explainable artificial intelligence to predict 1-year survival after palliative radiotherapy (RT) for bone metastasis.
MATERIALS AND METHODS
Data collected in the multicentric PRAIS trial were extracted for 574 eligible adults diagnosed with metastatic cancer. The primary end point was the overall survival (OS) at 1 year (1-year OS) after the start of RT. Candidate covariate predictors consisted of 13 clinical and tumor-related pre-RT patient characteristics, seven dosimetric and treatment-related variables, and 45 pre-RT laboratory variables. ML models were developed and internally validated using the Python package. The effectiveness of each model was evaluated in terms of discrimination. A Shapley Additive Explanations (SHAP) explainability analysis to infer the global and local feature importance and to understand the reasons for correct and misclassified predictions was performed.
RESULTS
The best-performing model for the classification of 1-year OS was the extreme gradient boosting algorithm, with AUC and F1-score values equal to 0.805 and 0.802, respectively. The SHAP technique revealed that higher chance of 1-year survival is associated with low values of interleukin-8, higher values of hemoglobin and lymphocyte count, and the nonuse of steroids.
CONCLUSION
An explainable ML approach can provide a reliable prediction of 1-year survival after RT in patients with advanced cancer. The implementation of SHAP analysis provides an intelligible explanation of individualized risk prediction, enabling oncologists to identify the best strategy for patient stratification and treatment selection.
Topics: Humans; Machine Learning; Bone Neoplasms; Palliative Care; Male; Female; Prognosis; Aged; Middle Aged; Algorithms
PubMed: 38917384
DOI: 10.1200/CCI.24.00027 -
PloS One 2024Prostate stem cell antigen (PSCA) is associated with disease progression, promotion of angiogenesis, invasion, metastasis and immune evasion in cancer. However, its...
Prostate stem cell antigen (PSCA) is associated with disease progression, promotion of angiogenesis, invasion, metastasis and immune evasion in cancer. However, its expression pattern and diagnostic and prognostic potential have not been thoroughly analysed from a pan-cancer perspective. This study aimed to examine the effects of PSCA on the prognosis and inflammatory cell infiltration patterns of various cancer types. We analysed the relationship between PSCA expression and immunological subtypes in tumor microenvironment (TME) and the role of molecular subtypes, potentially promising immune biomarkers and tumour-infiltrating lymphocytes (TILs) in various cancer types, especially lung adenocarcinoma (LUAD). In addition, we investigated the prognostic significance of PSCA expression in LUAD. The co-expression network of PSCA was found to be mainly involved in the regulation of immune responses and antigen processing and expression and was significantly enriched in pathological and substance metabolism-related pathways in cancer. Altogether, this study reveals that PSCA is a promising target for immunotherapy in patients with cancer.
Topics: Humans; Antigens, Neoplasm; Prognosis; Tumor Microenvironment; Lymphocytes, Tumor-Infiltrating; Neoplasm Proteins; GPI-Linked Proteins; Biomarkers, Tumor; Neoplasms; Adenocarcinoma of Lung; Lung Neoplasms; Gene Expression Regulation, Neoplastic; Male
PubMed: 38917176
DOI: 10.1371/journal.pone.0298469 -
JAMA Network Open Jun 2024Prostate cancer is a prevalent disease among men worldwide, exhibiting substantial heterogeneity in presentation and outcomes influenced by various factors, including... (Observational Study)
Observational Study
IMPORTANCE
Prostate cancer is a prevalent disease among men worldwide, exhibiting substantial heterogeneity in presentation and outcomes influenced by various factors, including race and ethnicity. Disparities in incidence, stage at diagnosis, and survival rates have been observed between Black men and those of other races and ethnicities.
OBJECTIVE
To compare prostate cancer outcomes between Black men and men with other race (Asian, Hispanic, Indigenous, Middle Eastern, White, Multiracial, and Other) in a universal health care system, with race and ethnicity self-reported.
DESIGN, SETTING, AND PARTICIPANTS
This was a prospective, observational cohort study of men diagnosed with prostate cancer between June 1, 2014, and August 28, 2023, who self-identified race and ethnicity. Participants included men who had been prospectively enrolled in the Alberta Prostate Cancer Research Initiative from the 2 major urology referral centers in Alberta (University of Alberta and University of Calgary). All men with prostate cancer enrolled in the initiative were included.
EXPOSURE
Race and ethnicity.
MAIN OUTCOMES AND MEASURES
The primary outcome was the stage and grade of prostate cancer at diagnosis. Further outcomes included age and prostate-specific antigen level at diagnosis, initial treatment modality, time from diagnosis to initial treatment, and prostate cancer-specific, metastasis-free, and overall survivals.
RESULTS
A total of 6534 men were included; 177 (2.7%) were Black, and 6357 (97.3%) had another race or ethnicity. Men who identified as Black were diagnosed with prostate cancer at an earlier age (mean [SD], 62.0 [8.2] compared with 64.6 [7.7] years; P < .001) and had a lower Charlson Comorbidity Index rating (14% compared with 7% ≤ 1; P < .001) compared with men of other races. Men who identified as Black had similar prostate-specific antigen levels at diagnosis, TNM category (74% vs 74% with T1-T2; P = .83) and Gleason Grade Group (34% compared with 35% Gleason Grade Group 1; P = .63). Black men had similar rates of prostate cancer-specific (hazard ratio [HR], 1.10; 95% CI, 0.41-2.97; P = .85), metastasis-free (HR, 0.88; 95% CI, 0.42-1.46; P = .44), and overall (HR, 0.55; 95% CI, 0.25-1.24; P = .15) survival.
CONCLUSIONS AND RELEVANCE
The findings of this cohort study suggest that Black men, despite being diagnosed at a younger age, experience comparable prostate cancer outcomes compared with men of other races.
Topics: Male; Humans; Prostatic Neoplasms; Aged; Middle Aged; Prospective Studies; Alberta; Canada; Black or African American; Neoplasm Grading; Black People; Neoplasm Staging; Prostate-Specific Antigen
PubMed: 38916889
DOI: 10.1001/jamanetworkopen.2024.18475 -
Aging Jun 2024Metastasis is the primary cause of cancer-related deaths, and colorectal cancer (CRC) liver metastasis is a major poor prognostic factor in CRC. NAT1...
Metastasis is the primary cause of cancer-related deaths, and colorectal cancer (CRC) liver metastasis is a major poor prognostic factor in CRC. NAT1 (N-acetyltransferase 1) plays a crucial role in the invasive and metastatic processes of colorectal cancer. The role and molecular mechanism of NAT1 on tumor cells were verified by establishing a cell model of overexpression and knockdown of NAT1, and further verified by establishing a liver metastasis model of colorectal cancer for animal experiments. and experiments have demonstrated that overexpression of NAT1 reduces the ability of metastasis and invasion of colorectal cancer cells. NAT1 overexpression inhibits the PI3K/AKT/mTOR signaling pathway, thereby suppressing the EMT (epithelial-mesenchymal transition) process and glycolytic ability of tumor cells. Additionally, decreased glycolytic ability results in reduced VEGF (Vascular endothelial growth factor) expression in colorectal cancer cells. The decreased VEGF expression leads to decreased angiogenesis and vascular permeability in liver metastases, ultimately reducing the occurrence of liver metastasis. Our findings highlight that overexpression of NAT1 significantly inhibits the PI3K/AKT/mTOR signaling pathway, thereby suppressing EMT, glycolytic ability, and VEGF expression in colorectal cancer cells, collectively preventing the development of liver metastasis.
PubMed: 38916406
DOI: 10.18632/aging.205957 -
Microbiology Spectrum Jun 2024is a microaerophilic Gram-negative bacterium that resides in the human stomach and is classified as a class I carcinogen for gastric cancer. Numerous studies have...
is a microaerophilic Gram-negative bacterium that resides in the human stomach and is classified as a class I carcinogen for gastric cancer. Numerous studies have demonstrated that infection plays a role in regulating the function of host cells, thereby contributing to the malignant transformation of these cells. However, infection is a chronic process, and short-term cellular experiments may not provide a comprehensive understanding of the situation, especially when considering the lower oxygen levels in the human stomach. In this study, we aimed to investigate the mechanisms underlying gastric cell dysfunction after prolonged exposure to under hypoxic conditions. We conducted a co-culture experiment using the gastric cell line GES-1 and for 30 generations under intermittent hypoxic conditions. By closely monitoring cell proliferation, migration, invasion, autophagy, and apoptosis, we revealed that sustained stimulation under hypoxic conditions significantly influences the function of GES-1 cells. This stimulation induces epithelial-mesenchymal transition and contributes to the propensity for malignant transformation of gastric cells. To confirm the results, we conducted an experiment involving Mongolian gerbils infected with for 85 weeks. All the results strongly suggest that the Nod1 receptor signaling pathway plays a crucial role in -related apoptosis and autophagy. In summary, continuous stimulation by affects the functioning of gastric cells through the Nod1 receptor signaling pathway, increasing the likelihood of cell carcinogenesis. The presence of hypoxic conditions further exacerbates this process.IMPORTANCEDeciphering the collaborative effects of infection on gastric epithelial cell function is key to unraveling the development mechanisms of gastric cancer. Prior research has solely examined the outcomes of short-term stimulation on gastric epithelial cells under aerobic conditions, neglecting the bacterium's nature as a microaerophilic organism that leads to cancer following prolonged stomach colonization. This study mimics a more genuine infection scenario by repeatedly exposing gastric epithelial cells to under hypoxic conditions for up to 30 generations. The results show that chronic exposure to in hypoxia substantially increases cell migration, invasion, and epithelial-mesenchymal transition, while suppressing autophagy and apoptosis. This highlights the significance of hypoxic conditions in intensifying the carcinogenic impact of infection. By accurately replicating the gastric environment, this study enhances our comprehension of 's pathogenic mechanisms in gastric cancer.
PubMed: 38916312
DOI: 10.1128/spectrum.00311-24 -
BioRxiv : the Preprint Server For... Jun 2024The receptor tyrosine kinase EphA2 drives cancer malignancy by facilitating metastasis. EphA2 can be found in different self-assembly states: as a monomer, dimer, and...
The receptor tyrosine kinase EphA2 drives cancer malignancy by facilitating metastasis. EphA2 can be found in different self-assembly states: as a monomer, dimer, and oligomer. However, our understanding remains limited regarding which EphA2 state is responsible for driving pro-metastatic signaling. To address this limitation, we have developed SiMPull-POP, a single-molecule method for accurate quantification of membrane protein self-assembly. Our experiments revealed that a reduction of plasma membrane cholesterol strongly promoted EphA2 self-assembly. Indeed, low cholesterol caused a similar effect to the EphA2 ligand ephrinA1-Fc. These results indicate that cholesterol inhibits EphA2 assembly. Phosphorylation studies in different cell lines revealed that low cholesterol increased phospho-serine levels, the signature of oncogenic signaling. Investigation of the mechanism that cholesterol uses to inhibit the assembly and activity of EphA2 indicate an in-trans effect, where EphA2 is phosphorylated by protein kinase A downstream of beta-adrenergic receptor activity, which cholesterol also inhibits. Our study not only provides new mechanistic insights on EphA2 oncogenic function, but also suggests that cholesterol acts as a molecular safeguard mechanism that prevents uncontrolled self-assembly and activation of EphA2.
PubMed: 38915729
DOI: 10.1101/2024.06.10.598255