Nutritional-immune status and physical activity (PA) are key to prognosis in cancer survivors, yet their joint association with mortality remains unclear. Therefore, we examined the independent and combined effects of PA and the Prognostic Nutritional Index (PNI) on mortality outcomes.

We evaluated the independent and joint associations of PA and PNI with all-cause, cancer-specific, non-cancer, and cardiovascular mortality among 2420 US cancer survivors using data from the 2007-2016 National Health and Nutrition Examination Survey (NHANES). Prognostic Nutritional Index was used as an indicator of nutritional-immune status. We used multivariable Cox regression, extended Cox regression models, and restricted cubic spline analyses to evaluate the associations and dose-response relationships. Combined associations were examined using joint PNI-PA exposure models and Kaplan-Meier curves; multiplicative interaction was tested with likelihood ratio tests, and additive interaction was quantified using relative excess risk due to interaction (RERI), attributable proportion (AP), and synergy index (SI). Sensitivity analyses were performed using median and tertile PNI cut-off points. Meanwhile, subgroup analyses were conducted to investigate heterogeneity.

Prognostic Nutritional Index was overall inversely associated with mortality risk (all-cause: HR = 0.762, cancer-specific: HR = 0.741, non-cancer: HR = 0.771, cardiovascular mortality: HR = 0.798; all p < 0.001), but this protective association was not constant and gradually attenuated over follow-up time. There was a graded inverse association between PA and mortality. Joint analyses revealed that the group with high PNI and sufficient PA was linked to an approximately 70% lower risk of all-cause mortality (p < 0.01). No multiplicative interaction was detected, whereas additive interaction was observed for all-cause mortality (RERI = 0.52; AP = 0.23; SI = 1.69). Sensitivity analyses supported the practical utility of PNI categorization, and subgroup analyses highlighted potentially heterogeneous associations across cancer types.

Prognostic Nutritional Index and PA were independently and jointly associated with survival among cancer survivors, supporting integrated survivorship strategies targeting nutritional-immune status and physical activity.

Large B-cell lymphoma (LBCL) is the most common lymphoma subtype, with diffuse LBCL (DLBCL) accounting for 30%-40% of new lymphoma cases. The International Prognostic Index (IPI) is widely used for prognostic assessment in DLBCL. Clinical features associated with a poorer prognosis, such as advanced disease stage, could be a consequence of delayed diagnosis, which in turn may be influenced by a patient's socioeconomic status. While healthcare in Finland aims to ensure equal access to timely and high-quality treatment for all, disparities still exist. In this study we evaluated the impact of patients' socioeconomic status on their access to diagnostic procedures.

Patient data was prospectively collected from seven hospitals between October 2014 and March 2020 in Finland. A total of 160 patients provided information regarding their diagnostic pathway and socioeconomic status via questionnaire. The data was combined with clinical data from patient records.

The symptoms to treatment interval (STI) varied between age groups (p = 0.019), marital status groups (p = 0.023), and healthcare providers. In addition, age, income level, and occupational status (all p < 0.001) influenced which healthcare provider patients used as their first place of contact.

In this prospective study, we analyzed the impact of patients' socioeconomic status on treatment delays within the treatment pathway. Socioeconomic status was found to have a significant effect on these delays. The delays varied not only between different socioeconomic groups but also across different healthcare providers.

Gastrointestinal (GI) cancers account for over one-quarter of global cancers, with marked regional variation in site distribution. In Egypt, contemporary data from large urban referral centres remain limited, particularly outside population-based cancer registries.

A hospital-based retrospective review was conducted of patients diagnosed with GI cancers at Alexandria Main University Hospital between 2010 and 2019. Age, sex, residence, year of diagnosis, and cancer site were analysed using SPSS and Joinpoint regression to assess temporal trends in hospital-registered case counts. Sensitivity analyses examined yearly proportions of GI cancers relative to all cancers to account for fluctuations in hospital volume.

Among 21,949 cancers registered during the study period, 3,995 (18.2%) were GI cancers. Colorectal and liver cancers were the most frequently registered GI sites, followed by pancreatic cancer. Using raw counts, overall hospital-registered GI cancer trends showed no statistically significant change across the decade. Small intestinal cancers demonstrated a significant decline in hospital-registered cases during 2015-2019 (annual percent change = - 22.2%; 95% CI - 64.8 to - 5.8; P = 0.019). The mean age at diagnosis was 55.1 ± 12.2 years, and 27.4% of cases were early-onset (< 50 years). Joinpoint analysis by age-onset category showed a significant increase in late-onset cases, while early-onset cases declined after 2014. Males predominated overall (male-to-female ratio 1.38:1), particularly in liver cancers (2.71; 95% CI 2.40-3.10). Patients residing in Alexandria more frequently presented with colorectal and gastric cancers, whereas liver cancers were more common among patients residing outside Alexandria. Sex-specific Joinpoint analyses for major GI cancer sites showed no statistically significant temporal changes.

GI cancers represent a substantial proportion of hospital-registered malignancies at Alexandria Main University Hospital, with largely stable case-count trends over the past decade. Sensitivity analyses suggest that relative burden may change even when absolute counts appear stable. These findings reflect hospital presentation patterns rather than population incidence and highlight the need for expanded population-based cancer registration and regional surveillance in Egypt.

Good's syndrome (GS), a rare immunodeficiency disorder characterized by thymoma and hypogammaglobulinemia, presents diagnostic and therapeutic challenges due to recurrent infections. We report a 53-year-old male farmer with GS complicated by recurrent pulmonary infections and COVID-19. Initial management focused on antiviral/anti-infective therapy and corticosteroids, but persistent hypogammaglobulinemia, B-cell depletion, and thymoma history were overlooked. Diagnosis was confirmed upon integrating the thymoma history, immunological profiling, and bronchial alveolar lavage-next generation sequencing, revealing Pneumocystis jirovecii and Herpes Simplex Virus-1 coinfections. Treatment with intravenous immunoglobulin loading dose (2 g/kg), pathogen-targeted therapy (voriconazole, cotrimoxazole), and tapered corticosteroids achieved clinical remission, with immunoglobulin G (IgG) elevating to 6.35 g/L. This case underscores the necessity of a "four-dimensional early warning system" integrating thymoma history, immune, imaging, and pathogen for timely GS diagnosis. Multidisciplinary collaboration and personalized regimens combining immunoglobulin replacement, precision anti-infectives, and immunomodulation are pivotal for optimizing outcomes in GS patients with complex infections.

Tumor microenvironment modulators have produced durable effects in cancer treatment. Targeting immune checkpoint receptors, such as PD-L1, has demonstrated efficacy in eliciting antitumor responses. However, resistance to immune checkpoint blockers (ICBs) has constrained the efficacy of these therapies. Previous studies showed a link between the expression of AXL receptor tyrosine kinase and resistance to ICBs. Therefore, designing combination treatments with synergistic mechanisms to overcome ICB-based resistance is needed. In addition to antibody-based therapies, gene silencing with siRNAs has recently been explored to alter the cancer environment to enhance the immune response. In this study, we targeted PD-L1 using an siRNA and AXL using a blocker (R428) in OVACAR-3 and CaSki cells, ovarian and cervical cancer cell lines, respectively, in the following groups: Scramble-siRNA, PD-L1-siRNA, Scramble-siRNA in conjunction with R428, PD-L1-siRNA in conjunction with R428, R428 monotherapy and untreated controls. Cell viability was assessed by MTT assay after 48 hours of treatment, and cisplatin sensitization was evaluated in resistant OVACAR-3 cells. Gene expression was analyzed by qRT-PCR, while flow cytometry quantified CD44+PD-L1+ populations, apoptosis (Annexin V/PI), and cell cycle distribution. The results showed a significant decrease in cell proliferation, suppression of EMT-regulating genes, reduction of stemness in cancer cells, increased apoptosis and disruption of the cell cycle in the studied cell lines. These findings suggest that simultaneous blockade of PD-L1 and AXL could serve as a novel tumor-suppressive strategy, especially for cancer patients resistant to ICBs.

Breast cancer remains a significant global health challenge, necessitating the development of innovative therapeutic strategies. This study aims to integrate immunotherapy and suicide gene therapy for breast cancer treatment. The cytokines IL-2 and GM-CSF, which are crucial in orchestrating immune responses against cancer, are the focal points of investigation. This study focused on the co-expression of these cytokines alongside apoptin, a promising protein derived from chicken anemia virus, via the bidirectional survivin promoter (pAIG). The constructed vectors were transfected into MCF-7 cells, which resulted in a significant increase in gene expression. Compared with individual cytokine and apoptin vectors (pIG and pA), the pAIG vector exhibited superior efficacy, reducing cell viability and inducing apoptosis (31.7%) at 72 h post-transfection. Exploration of the interaction of apoptin revealed its association with the human PIK3R1 protein, which interacts with both cytokines, contributing to the inhibition of cell viability. Leveraging the survivin promoter for co-expression presents a promising avenue for targeted breast cancer gene therapy, potentially disrupting intricate signaling networks involved in cancer progression. This study provides valuable insights into the synergistic effects of IL-2, GM-CSF, and apoptin co-expression, offering a compelling approach to advancing breast cancer treatment. These findings contribute to the broader landscape of cancer gene therapy, emphasizing the potential of combining immunomodulatory agents and gene-directed approaches to improve therapeutic outcomes.

Breast cancer is a major cause of cancer-related mortality among women, with hormone receptor-positive (HR+) breast cancer accounting for 70-80% of diagnosed cases. The current treatment approaches include both endocrine monotherapy and combinational strategies incorporating targeted signaling pathway inhibitors. Despite recent therapeutic advances that have significantly improved patient outcomes, the development of resistance to endocrine therapies leads to relapses and treatment failure. Emerging evidence has shown that long non-coding RNAs (lncRNAs) are therapeutic modulators; however, their involvement in clinical studies has not been much explored. In HR+ breast cancer, lncRNAs influence both sensitivity and resistance to endocrine therapy by modulating estrogen receptor (ER) function, switching between alternative survival pathways, and altering tumor epigenetics and tumor microenvironment. The major focus of this comprehensive review is to understand the role of lncRNAs in overcoming the endocrine resistance issues in the treatment of HR+ breast cancer. It presents a comprehensive approach focused on endocrine therapy mechanisms, resistance, and adaptive escape pathways of HR+ tumor cells. By mapping these mechanisms of endocrine therapy, the review reveals novel therapeutic targets for the treatment of HR+ breast cancer. Lastly, it highlights the specialized lncRNA-based therapeutics for bone metastatic niches in HR+ breast cancer and current approaches of therapeutic targeting of lncRNAs for disease treatment.

Tumor drug resistance remains a significant challenge in the failure of cancer treatments, rooted in the complex dynamic adaptive evolution of tumors within the triad of "cell-microenvironment-host." Previous research methodologies have often concentrated on single-level mechanisms, such as gene mutations or alterations in specific signaling pathways, while neglecting the intricate interactions among tumors, their microenvironments, and the host. This paper proposes a novel theoretical framework-the "Dynamic Ecosystem of Tumor Resistance"-which integrates three levels: intrinsic tumor cell heterogeneity and plasticity, microenvironment interactions, and host systemic regulatory factors. The objective is to systematically explore key resistance mechanisms and their dynamic interactions across these levels, thereby elucidating the complex nature of resistance. This framework aims to stimulate further research into therapeutic strategies targeting tumor resistance and to provide novel insights for the development of clinical approaches to treating malignant tumors.

Intrahepatic cholangiocarcinoma (ICC) is a lethal malignancy frequently characterized by intrinsic resistance to standard gemcitabine (Gem) chemotherapy. This study aimed to investigate whether andrographolide (Andro) could sensitize intrinsically gemcitabine-resistant ICC cells to gemcitabine and to explore the underlying molecular mechanisms.

Naturally Gem-resistant ICC cell lines (HUCCT-1 and QBC-939) were treated with Andro, Gem, or their combination. Synergistic effects were quantified using the Chou-Talalay method. Anti-tumor efficacy was assessed via CCK-8, colony formation, EdU incorporation, wound healing, and Transwell invasion assays. ROS accumulation, apoptosis, mitochondrial membrane potential, and cell-cycle distribution were assessed by fluorescence microscopy and flow cytometry, as appropriate. Molecular targets were identified using molecular docking, RT-qPCR, and Western blotting.

Andro and Gem exhibited strong synergistic anti-tumor activity (Combination Index < 1.0) in both cell lines. The combination significantly suppressed proliferation, motility, and epithelial-mesenchymal transition. Mechanistically, the synergy was driven by a surge in intracellular ROS, triggering mitochondrial apoptosis and G1/S phase arrest. Furthermore, Ribonucleotide-diphosphate reductase subunit M2 was identified as a candidate molecular target associated with the effects of andrographolide, leading to its downregulation and the subsequent inactivation of the JAK/STAT3 signaling pathway.

Andrographolide overcomes intrinsic Gem resistance in ICC, potentially through modulation of the RRM2/JAK/STAT3 axis. This combination therapy represents a promising strategy for treating chemoresistant intrahepatic cholangiocarcinoma.

Cancer is associated with a prothrombotic state and venous thromboembolism (VTE) can be the first manifestation of occult cancer. However, no impact on survival of extensive cancer screening in VTE has been demonstrated. Limited data are available on the association between D-dimer (DD), a non-specific marker of activation of coagulation, at VTE diagnosis and occult cancer. The objective is to investigate whether high DD levels at VTE diagnosis are associated with subsequent cancer development. The study design is a retrospective cohort study conducted in a single tertiary care hospital from 2008 to 2018. The participants were consecutive patients diagnosed with symptomatic VTE and without known overt cancer who underwent routine clinical evaluation and laboratory tests. In case of abnormal findings, further targeted tests were performed. The primary outcome measures were cancer development within 12 months of VTE diagnosis. 843 patients (413 women-49%, median age 67.3 years; 10 lost to follow-up-1.2%) were included, of whom 567 (67%) had unprovoked VTE. Median DD was 2,750 ng/mL (range 30-45,320) and DD was above 8,000 ng/mL in 151 patients (18%). During follow-up, 37 patients (all above 60 years) developed new cancers (4.6 percent patient years; 95%CI 3.3-6.3). Multivariate regression showed that age above 60 years (Hazard Ratio-HR 11.7; 95%CI 1.58-86.6; p = 0.016) and DD above 8,000 ng/mL (HR: 2.5; 95%CI 1.22-5.24; p = 0.012) were independently associated with subsequent cancer development. Patients older than 60 years at VTE diagnosis may deserve extensive screening for occult cancer, and DD above 8000 ng/mL may be an index of occult cancer.