Search Results (4,820)

Background: Pyrotinib, an irreversible pan-HER tyrosine kinase inhibitor, has demonstrated substantial clinical efficacy in patients with HER2-positive breast cancer (BC). However, intrinsic and acquired resistance remain important challenges limiting therapeutic benefit, and reliable biomarkers for predicting pyrotinib response are currently unavailable. This study aimed to identify molecular determinants associated with pyrotinib resistance and uncover their underlying mechanisms. Methods: Pre-treatment tumour samples from an exploratory discovery cohort of 12 patients with HER2-positive BC receiving pyrotinib-containing neoadjuvant therapy were analysed by proteomic profiling. Differentially expressed proteins (DEPs) between the pathological complete response (pCR) and non-pCR groups were integrated with weighted gene co-expression network analysis and protein–protein interaction network analysis to identify candidate proteins. The prognostic relevance of the candidate genes was subsequently evaluated using 127 machine-learning strategies across three independent BC cohorts. Models were ranked according to the mean area under the receiver operating characteristic curve (AUC) across two evaluation cohorts, and SHapley Additive exPlanations (SHAP) analysis was performed separately in both cohorts to prioritise a candidate for subsequent investigation. In vitro and in vivo experiments were then conducted to evaluate the biological role of the prioritised candidate and its association with pyrotinib sensitivity. Finally, the association between pre-treatment SLC27A2 expression and pCR was evaluated in an independent, non-overlapping retrospective cohort of 103 patients receiving pyrotinib-containing neoadjuvant therapy. Results: Exploratory proteomic profiling of 12 pre-treatment tumour samples identified 617 DEPs between the pCR and non-pCR groups. Among 127 machine-learning strategies used to evaluate the prognostic relevance of the candidate genes, the glmBoost–random forest model achieved the highest mean AUC across the two evaluation cohorts (mean AUC = 0.678). SHAP analysis showed that SLC27A2 ranked second in GSE16446 and first in GSE48390 according to mean absolute SHAP values, supporting its prioritisation for subsequent investigation. Functional experiments showed that SLC27A2 promoted proliferation, migration, invasion, and epithelial–mesenchymal transition in HER2-positive BC cells. SLC27A2 knockdown enhanced pyrotinib sensitivity in vitro. In the xenograft experiment using female BALB/c nude mice, both SLC27A2 knockdown and pyrotinib treatment reduced tumour growth, and a significant interaction between the two factors was observed for endpoint tumour weight (p for interaction = 0.041). Mechanistically, SLC27A2 knockdown reduced lipid accumulation and PPARα expression, whereas pharmacological activation of PPARα partially attenuated the increase in pyrotinib sensitivity induced by SLC27A2 knockdown. Clinical validation further showed that high-pre-treatment SLC27A2 expression was independently associated with a lower likelihood of achieving pCR after pyrotinib-containing neoadjuvant therapy (OR = 0.10, 95% CI: 0.03–0.31, p < 0.001). Conclusions: SLC27A2 is a candidate factor associated with BC prognosis and reduced pyrotinib sensitivity in HER2-positive BC. Preclinical findings suggested that PPARα-related fatty acid metabolism may contribute to the association between SLC27A2 and pyrotinib response, while clinical validation showed that high-pre-treatment SLC27A2 expression was independently associated with a lower likelihood of achieving pCR following pyrotinib-containing neoadjuvant therapy. These findings support SLC27A2 as a candidate response-associated biomarker and potential therapeutic target, although further mechanistic investigation and external clinical validation are required. Full article

Cancer, the second leading cause of death worldwide, is a significant global challenge, and widespread, accessible, and early diagnostics are recognized as the most cost-effective strategies for reducing cancer burdens. Point-of-care (POC) systems offer an attractive alternative by enabling rapid and cost-effective diagnoses. We introduce a novel POC strategy for cancer biomarker identification based on monitoring the isothermal amplification of relevant cancer markers using a portable Arduino-based loop-mediated isothermal amplification (LAMP) system. The trajectory of the LAMP reaction during the first 3 min of the reaction is used as an indicator of the rate of amplification (defined as the m_P3 value). We obtained sets of m_P3 values that showed statistically significant differences in the genetic expression of four genes (ESR 1, PGR, Her2, and Ki67) within and between tissue spheroids derived from the MCF7, MDA-MB-231, Du145, and BJ fibroblast cell lines. We then used principal component analysis and clustering techniques to demonstrate that the m_P3 value sets derived from the expression of the four selected genes are sufficient to distinguish tissue spheroids derived from four different commercial cell lines. Further qPCR and immunostaining assays confirmed the quantitative LAMP (qLAMP) experimental trends. The immunostaining results were consistent with previous literature reports and with our qLAMP and qPCR results. We present a proof-of-concept demonstration of the use of a LAMP-based POC platform for the identification or discrimination of cancer tissues. Our strategy can be extended to other diseases associated with altered gene expression in body tissues or fluids. Full article

Background: In recent decades, the incidence of colorectal cancer (CRC) has been rising worldwide. CRC ranks second in cancer-related mortality. The identification of reliable biomarkers for early diagnosis and prognosis prediction, along with a deeper understanding of the underlying molecular events, holds substantial promise for improving patient outcomes. The tissue inhibitor of the metalloproteinase 1 (TIMP1) gene is overexpressed in various gastrointestinal malignancies and contributes to tumor progression. However, its role in regulating the CRC tumor immune microenvironment (TIME) and its potential as a clinically actionable prognostic biomarker remain unclear. Methods: To probe how TIMP1 acts as a prognosis-related candidate biomarker in colorectal carcinoma, TCGA-derived datasets were adopted to conduct Kaplan–Meier survival assessment. We also investigated the connection between the expression abundance of TIMP1 and the infiltration of immune populations and intratumoral lymphocytes; furthermore, immune checkpoint-related genes were systematically assessed across multiple tumor types via the TISIDB and TIMER2.0 platforms, with particular emphasis on CRC. We adopted the ESTIMATE scoring system to figure out how TIMP1 gene expression correlates with the phenotypic properties of the colorectal-cancer TIME. We relied on the limma toolkit for the screening of differential transcripts from high-TIMP1 and low-TIMP1 cohorts. Enrichment assessments covering Gene Ontology terms and Kyoto Encyclopedia of Genes and Genomes entries were then carried out to predict the potential biological pathways associated with TIMP1. We constructed the protein–protein interaction map for TIMP1-interacting partners via the STRING repository. To further explore TIMP1-correlated genes, we performed Venn diagram intersection analysis combined with Spearman’s correlation test. Finally, quantitative reverse-transcription PCR was then implemented to detect TIMP1 messenger-RNA abundance inside the RKO colorectal carcinoma cell line as well as normal colonic epithelial CCD-18Co cells, which offered in vitro experimental verification for our bioinformatic outcomes. Results: According to outcome data, TIMP1 transcripts were markedly up-regulated in CRC specimens and cell lines relative to normal samples. Elevated TIMP1 expression served as a poor-prognosis indicator for overall survival (hazard ratio [HR] = 0.43, 95% confidence interval [CI] = 0.29–0.64, p < 0.001) and disease-specific survival (HR = 0.39, 95% CI = 0.22–0.68, p = 0.001) among colorectal-carcinoma patients. TIMP1-high and TIMP1-low groups exhibited notable differences in immune cell infiltration (CD8⁺ T, macrophage, mast, neutrophil, B, monocyte, dendritic, and CD4⁺ T cells). TIMP1 expression was also significantly correlated with tumor-infiltrating lymphocytes, key immune checkpoint genes (e.g., CD274 [PD-L1] and CTLA4), and immunomodulatory chemokines (e.g., CCL3 and CCL5). Twelve TIMP1-interacting DEGs were selected: COL5A1, FN1, PRG4, and a cluster of nine MMPs (MMP1/2/3/7/8/9/11/13/14), all of which showed significant positive correlations with TIMP1 (r = 0.31–0.63, all p < 0.001). Conclusions: TIMP1 expression correlates with features of the tumor immune microenvironment and extracellular matrix remodeling in CRC, suggesting that TIMP1 shows potential as a candidate biomarker. However, its potential as a therapeutic target warrants further experimental investigation. Full article

Background: Skin cancer encompasses a diverse range of malignancies and remains a significant global health challenge. Accurate machine-learning-assisted diagnosis can substantially improve patient outcomes through early detection and timely clinical intervention. Federated Learning (FL) enables privacy-preserving collaborative model training across multiple healthcare institutions while ensuring that sensitive patient data remain decentralized. However, deploying advanced architectures such as Vision Transformers (ViTs) in clinical environments is challenging due to the high computational demands of self-attention mechanisms. Methods: This work proposes FedSwin-LHTP, an efficient federated learning framework for skin lesion classification that integrates a Swin Transformer backbone with a Lightweight Hessian-Inspired Token Pruning (LHTP) mechanism. LHTP estimates token importance using a second-order Taylor approximation around converged local model parameters to identify less informative patch tokens, enabling the early pruning of redundant representations without explicitly computing the Hessian matrix. Furthermore, the framework incorporates the FedProx optimization objective to mitigate client drift under heterogeneous non-IID data distributions. The proposed framework is evaluated on the HAM10000 and ISIC datasets under realistic non-IID federated settings. Results: Experimental results demonstrate stable convergence, effective knowledge aggregation, and robust diagnostic discrimination across distributed clients. By adaptively pruning approximately 60% of Stage-1 tokens, the proposed framework substantially reduces the computational burden of local transformer processing while maintaining high multiclass classification performance, achieving an accuracy of up to 96.1% on the evaluated datasets. Conclusions: These results highlight the potential of FedSwin-LHTP as a practical, privacy-preserving, and resource-efficient solution for collaborative healthcare intelligence. Full article

Background and objectives: Melanoma survivors may develop additional primary malignancies, but data from Eastern European hospital cohorts are scarce. We aimed to estimate the observed incidence of second primary cancers (SPCs) within a Romanian referral-centre cohort, identify associated factors, and explore the association of SPC occurrence with overall survival. Methods: We conducted a retrospective, hospital-based cohort study of 394 patients with histopathologically confirmed cutaneous melanoma followed at two referral centres in Cluj-Napoca. Additional malignancies were counted as new primaries only when clinical and/or histopathological documentation distinguished them from recurrence or metastasis. Incidence density was expressed per 1000 person-years. Multivariable logistic regression assessed age, sex, residence, and Breslow thickness. Fixed-covariate Cox and Kaplan–Meier analyses were considered exploratory because of immortal-time and competing-risk limitations. Results: Over 1848 person-years, 79 patients (20.1%) developed at least one SPC (131 events; observed incidence 70.9/1000 person-years), most frequently cutaneous (53.6/1000 person-years). SPC occurrence increased with age (Cochran–Armitage Z = 5.63, p < 0.001); the Kaplan–Meier complement estimate reached 20.7% at five years. Age independently predicted SPC (OR 1.86 per decade, p < 0.001), whereas greater Breslow thickness was inversely associated (OR 0.86, p = 0.008). Actinic keratosis showed a strong unadjusted association (OR 6.64, p < 0.001) but was not included in the adjusted model. The fixed-status Cox model showed lower mortality among patients with an SPC (HR 0.36, p < 0.001), a finding vulnerable to detection and immortal-time bias. Conclusions: SPCs were frequent in this hospital cohort and predominantly cutaneous. Older age was an independent predictor, while actinic keratosis was a strong unadjusted marker. Prospective, population-based validation is needed before surveillance intensity is individualised. Full article

Systemic lupus erythematosus (SLE) is a multifaceted autoimmune disease characterized by immune tolerance breakdown, immune cell dysfunction, and chronic inflammation. Cancer is a serious health problem and the second leading cause of mortality worldwide. Emerging evidence underscores the key role of metabolic dysregulation and the association with immunity and immune-related complications in cancer and SLE. Enhanced glycolysis and OXPHOS have been repeatedly reported in both diseases. Metabolic reprogramming is common in cancer cells and immune cells of SLE patients. In many cases, cancer cells and B cells rely on fatty acid oxidation to generate energy. Accordingly, key enzymes in those processes are also upregulated. This review summarizes current findings on major common metabolic dysregulation in cancer and SLE, highlighting the interplay of metabolic disturbances, mitochondrial dysfunction and disease pathogenesis. Furthermore, we explore the potential of targeting metabolic pathways as a therapeutic strategy to mitigate organ damage and improve outcomes in patients with SLE or cancer. We will also discuss the hurdles and prospective developments in metabolism-targeted therapy. We hope this review inspires collaborative work between cancer researchers and SLE clinicians and facilitates clinical application of cancer-metabolism-targeted drug in SLE patients. Full article

Protein arginine methyltransferase 5 (PRMT5) is a synthetic lethal target in methylthioadenosine phosphorylase-deleted (MTAP-null) cancers. Second-generation methylthioadenosine (MTA)-cooperative PRMT5 inhibitors preferentially target MTAP-null cells while largely sparing MTAP-wildtype (MTAP-WT) cells, thereby improving tumor selectivity over first-generation PRMT5 inhibitors. Despite encouraging efficacy and safety signals in early clinical studies, the modest objective response rates (ORRs) observed with these inhibitors suggest that intrinsic or acquired resistance may limit their clinical benefit. Here, we investigated acquired resistance to the MTA-cooperative PRMT5 inhibitor BMS-986504/MRTX1719 in MTAP-null non-small cell lung cancer (NSCLC) cells and sought to identify therapeutic vulnerabilities that emerge upon resistance. Using multiple in vitro-derived resistant models, we found that acquired resistance was accompanied by cross-resistance to mechanistically distinct PRMT5 inhibitors. Notably, this phenotype was not fully explained by altered PRMT5 activity or changes in MTA levels. High-throughput drug screening of paired sensitive and resistant cells revealed increased sensitivity to MEK inhibitors following acquisition of MRTX1719 resistance in KRAS-wildtype NSCLC cells. Consistently, resistant cells exhibited rewired MAPK-related transcriptional programs. Together, these findings identify MEK inhibition as a reproducible collateral vulnerability associated with acquired MRTX1719 resistance in MTAP-null NSCLC models and support further evaluation of MEK inhibition as a potential treatment-switching strategy following resistance. Full article

Background/Objectives: The COVID-19 pandemic was a major challenge for healthcare systems and social life worldwide. During the pandemic, studies focused on examining structural changes in patient care and establishing new guidelines to manage COVID-19, but very few of them addressed patients’ perceptions and concerns regarding changes in cancer treatment during the pandemic. This study aimed to assess the changes in their therapy situation during three waves of the pandemic and the impact on their social life. Methods: This exploratory cross-sectional multicenter survey was conducted among patients with gynecological malignancies and breast cancer at gynecological oncology centers in Germany between October 2020 and February 2022. An anonymous paper-based 50-item questionnaire, available in German, assessed medical care, treatment modifications, mental health, and socioeconomic burden during the COVID-19 pandemic. Data were analyzed descriptively. Two subgroup analyses were conducted, comparing age groups ≤70 and >70 years, as well as patients with and without a migrant background. Results: Overall, 778 patients met the inclusion criteria of the survey (median age: 59; range: 24–93). In the majority of the patients (77.1%), the treatment schedules remained unchanged during COVID-19 pandemic. Treatment appointments were modified in a small number of patients (9.0%). Changes in therapy schedules were slightly more common among the second- and third-generation migrants and among patients ≤70 years. Despite the uncertainty of the COVID-19 pandemic, most patients (83.4%) kept their trust in the healthcare system. Acceptance of preventive measures was high, and 85.9% were willing to be vaccinated against COVID-19. Psychological symptoms such as worries and fear were reported by more than half of the participants during the last 2 weeks previous to the survey and more common among patients ≤70 years. Only 8.6% were more afraid of a COVID-19 infection than their cancer disease. Conclusions: Despite major challenges in cancer care due to the COVID-19 pandemic, access to cancer treatment and adequate management at gynecological oncology centers in Germany remained stable. The increased psychological burden in crises requires new infrastructure and should be addressed to improve patient care in future crises. The acceptance of taking preventive measures against COVID-19 was high among cancer patients. Full article

One respondent says antibiotics kill viruses. A second says they do not know. A third says cancer cures are hidden for profit. A standard literacy score counts all three as one deficit. This exploratory study asks whether they behave alike. In a July 2025 Romanian telephone survey (analytic N = 1007), six factual, two worldview-linked and two conspiratorial anti-science (CAS) items were analyzed separately, treating “don’t know” (DK) as a third response. The response patterns did not converge. Factor analysis of substantive answers retained two factors, not one, and the six-item core’s weighted internal consistency among answerers was 0.379. DK responding formed a coherent cross-item pattern, but less uniform than the full-sample alpha of 0.926 implies: it falls to 0.803 once the 135 all-DK respondents are set aside. CAS endorsement converged with generic conspiracist belief and tracked institutional distrust, where factual accuracy did not. Education and internet frequency mainly differentiated DK responding; economic security and democratic satisfaction were associated with lower CAS endorsement. Against Eurobarometer 95.2 (2021), Romanian factual accuracy sits about two items lower than the EU27 average excluding Romania, and CAS endorsement is roughly 1.7 times as high, in both Romanian waves. Uncertainty, error and conspiratorial belief remain conceptually distinct. Full article

Background/Objectives: The advent of immune checkpoint inhibitors (ICIs) and targeted therapies has revolutionized advanced melanoma treatment but introduced unique immune-related adverse events (irAEs). Hematological irAEs (Hem-irAEs) are rare but carry disproportionately high morbidity and mortality. This review systematically synthesizes current literature to comprehensively understand the incidence, pathophysiology, clinical presentation, and management of Hem-irAEs in modern melanoma therapy. Methods: A comprehensive Web of Science literature search (January 2015 to January 2026) identified studies reporting hematological adverse events associated with melanoma immunotherapy and targeted therapies. After screening 2274 records, 130 relevant studies were included for quantitative data extraction, focusing on incidence rates and toxicity grading. Results: Hem-irAEs occur infrequently (under 4% overall incidence for ICIs) but possess staggering mortality rates between 12% and 15.5%. The most common manifestations are immune thrombocytopenia (ITP), autoimmune hemolytic anemia, and neutropenia. Combination regimens significantly amplify toxicity frequency and severity. Diagnosis requires meticulous baseline monitoring and bone marrow biopsies to differentiate peripheral destruction from central marrow failure. First-line management mandates ICI discontinuation and high-dose corticosteroids, utilizing targeted second-line immunosuppressants for refractory syndromes. Conclusions: Hem-irAEs embody a profound clinical paradox: while mild toxicities often herald a robust anti-tumor response, severe hematological events drastically increase non-cancer mortality, negating these oncological benefits. Navigating this “double-edged sword” demands a paradigm shift toward proactive risk stratification. Integrating predictive biomarkers including baseline autoantibodies, Human Leukocyte Antigens (HLA) profiling, and systemic inflammatory indices is crucial to identify vulnerable populations before treatment. Optimizing outcomes requires highly personalized vigilance to balance the life-saving efficacy of immunotherapy against the catastrophic threat of hematopoietic failure. Full article

Background/Objectives: Glioblastoma (GBM) is the most lethal primary brain malignancy in adults, with a median overall survival of approximately 15 months. Temozolomide (TMZ) resistance develops in virtually all patients, and no second-line regimen has improved outcomes over the past two decades. The DNA methyltransferase inhibitor decitabine (DAC) has attracted interest as a chemosensitizer, but whether it directly reverses the TMZ-resistance transcriptome or operates through distinct, complementary mechanisms has not been tested at multi-omics resolution. Methods: We performed an integrative six-layer multi-omics analysis across five public GEO datasets (bulk RNA-seq, EPIC 850K methylation, and 21,676 single cells) re-purposed from studies conducted for unrelated aims, formally tested DAC-mediated reversal of the TMZ-resistance transcriptome across 11,707 genes, mapped pharmacogenomic targets with DGIdb v5, and built an exploratory, hypothesis-generating 11-gene prognostic model internally validated in TCGA-GBM (n = 166) and externally tested in the independent CPTAC-GBM cohort (n = 96). Results: DAC reprogrammed transcription across 1114–1882 differentially expressed genes per cohort and reactivated 146 direct epigenetic targets, identifying INPP5D/SHIP1 as the top-ranked direct epigenetic-reactivation target. Genome-wide reversal analysis across 11,707 co-detected genes showed a negligible effect (Spearman ρ = 0.073), but single-cell analysis revealed significant per-cell attenuation of MES-like and stem-like programs (Δ = −0.071 and −0.135, respectively; both p < 0.001). The 11-gene risk model achieved a Harrell’s C-index of 0.706 (apparent); after correcting for the two-stage gene selection with a full-pipeline bootstrap, the optimism-corrected C-index was 0.63, and external validation in an independent cohort (CPTAC-GBM, n = 96) showed only near-chance discrimination (C-index 0.55), indicating that the signature does not generalize and is exploratory. Pharmacogenomic mapping yielded 734 unique therapeutic agents (230 FDA-approved) across 69 druggable targets after excluding AR. Most of these agents are not GBM-directed, so this catalog-level mapping is hypothesis-generating rather than a set of therapeutic recommendations. Conclusions: DAC does not broadly reverse the TMZ-resistant transcriptome but acts through three complementary mechanisms: epigenetic reactivation of INPP5D/SHIP1, cancer-testis-antigen and type I interferon induction, and per-cell attenuation of mesenchymal–stem-like transcriptional intensity, supporting hypotheses for rationally designed DAC-based combination therapy in TMZ-resistant GBM. Full article

Breast cancer is the most common cancer among women, and early detection through mammography is essential for reducing mortality. Artificial intelligence can support radiologists by improving diagnostic accuracy. To develop and evaluate a two-stage ensemble machine learning pipeline for breast cancer diagnosis from digital mammograms. The proposed framework combines image preprocessing, multiple convolutional neural networks trained under different conditions, and a second-stage classifier that integrates the CNN outputs. Several machine learning models and feature selection techniques were evaluated using publicly available mammography datasets. Results: The ensemble approach consistently outperformed the individual CNN models. The MLP classifier achieved the best overall balance between precision and recall, while the heuristic fusion method provided the highest sensitivity. Feature selection reduced model complexity while maintaining comparable performance, and cross-validation confirmed the robustness of the proposed methodology. Combining complementary information from multiple CNNs with classical machine learning improves diagnostic performance and provides a robust framework for computer-aided breast cancer diagnosis. The proposed two-stage ensemble offers an effective and interpretable approach for mammographic breast cancer classification. A demonstration application incorporating Grad-CAM explainability further supports its potential use as a clinical decision-support tool. Full article

Background/Objectives: Patient education (PE) is a key component in the management of chronic conditions, including living with an entero-urostomy. Exploring patients’ and caregivers’ experiences may inform the development of tailored educational interventions. This study aimed to explore the perceptions, experiences, and needs of adult oncology patients with entero-urostomies and their caregivers as part of the patient education process. Methods: A descriptive qualitative study was conducted at a single Italian cancer centre using two focus group sessions integrated with PE activities. Discussions were audio-recorded and analysed through thematic analysis following the framework described by Dawadi. NVivo was used to support data management and facilitate the assessment of data saturation. Results: A total of 28 participants (15 patients and 13 caregivers) were recruited. Three main themes emerged: translational patient education as a co-constructed educational process, time as a protective and regulatory resource in everyday stoma management and living with a stoma requires adaptation and meaning-making. The first theme describes a dynamic integration of clinical, peer, and relational knowledge co-constructed by nurses, patients, and caregivers. The second theme referred to the perception of time and care contexts, including telenursing, as protective spaces supporting anticipatory coping and daily life planning. The last theme captured the embodied and psychological adaptation to living with a stoma, characterised by heterogeneous processes of acceptance and meaning-making. Conclusions: PE emerges as a relational and interactive process that supports self-care, emotional adjustment, and quality of life. The concept of translational patient education, as part of the patient education process, offers a novel framework for integrating multiple forms of knowledge within educational practices, strengthening the person-centred nature of PE programmes. These findings support the development of tailored, person-centred PE interventions that incorporate the dynamic educational ecosystem involving patients, caregivers, and stoma care nurses. They also highlight the need for further research to validate this conceptual model across diverse settings and populations. Full article

Background/Objectives: Colorectal cancer (CRC) is the second most common cancer-causing death in the United States. The Mediterranean diet, rich in extra-virgin olive oil (EVOO), is associated with a lower risk of colorectal cancer (CRC). Earlier studies reported S-(−)-oleocanthal (OC), the major EVOO phenolic, to be effective in CRC progression and recurrence suppression in a subcutaneous xenograft model by targeting the SMYD2–EZH2/c-MET signaling axis and favorably modulating gut microbiota (GM). However, lead validation in an orthotopically xenografted model that mimics the tumor microenvironment is yet to be achieved. The GM contribution to OC anti-CRC activity remains unknown. Methods: We used an orthotopic intra-cecally xenografted nude mouse model to validate OC anti-KRAS-mutant CRC activity and assessed the contribution of OC GM modulation to this activity using an oral antibiotic depletion strategy. Results: Daily oral 10 mg/kg OC impressively suppressed KRAS^G13D-mutant CRC HCT-116-Luc progression and metastasis more effectively than intraperitoneal administration 3×/week. By contrast, GM depletion with a broad-spectrum antibiotics cocktail (ABC) partially attenuated this activity, suggesting GM contribution to OC anti-CRC activity. Thus, fecal microbiota transplantation (FMT) was conducted using fresh daily oral fecal GM treatments collected from 20 mg/kg OC-dosed nude mouse donors. A week before FMT dosing, orthotopic HCT-116-Luc tumor-bearing recipient mice were subjected to GM depletion using daily oral ABC dosing. Recipient mice treated with FMT from OC-treated donors exhibited dramatic >99% reductions in primary and near-complete suppression of multi-organ metastatic tumor burden versus FMT controls. Conclusions: Collectively, oral OC is validated as an effective anti-KRAS^G13D-mutant CRC lead. Future clinical trials can validate its anti-CRC potential in a human model. Full article

Research Background: Breast cancer is a malignant tumor that threatens women’s health. Among breast cancer patients, about 4.2% to 17% may suffer from multiple primary malignant neoplasms. Cases of patients suffering from both breast cancer and multiple myeloma are relatively rare in clinical practice. This paper reports one case of a patient who developed multiple myeloma during the treatment of breast cancer. Clinical Data: The patient was a 56-year-old female, admitted to hospital due to “fever for 4 days, one year after the treatment of left breast cancer”. The patient was diagnosed with left breast cancer (ypT1N1M0, HER2-overexpressing subtype) approximately one year prior to presentation. Following diagnosis, the patient was treated sequentially with TcbHP and THP chemotherapy regimens, and subsequently received local radiotherapy. The patient developed fever four days prior to admission. Further laboratory examinations revealed pancytopenia, positive IgA-λ-type monoclonal immunoglobulin by immunofixation electrophoresis, and myeloma cells accounting for 11% in bone marrow smears. Bone marrow immunophenotyping indicated abnormal plasma cells, and pathological results of bone marrow biopsy were consistent with multiple myeloma. The final diagnosis was breast cancer complicated with multiple myeloma. After confirmed diagnosis, the patient was transferred to another hospital for targeted treatment of multiple myeloma and has been receiving continuous treatment there up to the time of follow-up. Conclusions: For patients with breast cancer, if they develop bone pain, anemia, hypercalcemia or renal dysfunction that cannot be explained by tumor metastasis or conventional complications after surgery or during follow-up, clinicians should be alert to the possibility of second primary tumors. Full article