• Neoadjuvant Chemotherapy in Choroid Plexus Carcinoma: Improving Surgical Safety and Resection Outcomes.
    3 weeks ago
    Choroid plexus carcinoma (CPC) is a rare and highly vascular malignant brain tumour that occurs mainly in children. Complete surgical resection offers the best chance of long-term survival, but this is often difficult due to excessive intraoperative bleeding. Preoperative (neoadjuvant) chemotherapy has been explored as a strategy to shrink the tumour and reduce its vascularity before surgery. In this review, we have summarized the available literature on preoperative chemotherapy in CPC and its effect on surgical outcomes. Reported cases and small series show that platinum- and etoposide-based regimens can decrease tumour size and intraoperative blood loss, allowing safer and more complete resections. However, due to the rarity of CPC and limited data, larger multicentre studies are required to validate these findings and establish standardized treatment protocols.
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  • Clinicopathological significance of perineural and lymphovascular invasion in oral and oesophageal squamous cell carcinoma: A retrospective study.
    3 weeks ago
    To determine the presence and association of perineural and lymphovascular invasion with different stages of oral and oesophageal squamous cell carcinoma, and to assess their relationship with lymph node metastasis in both types of tumours.

    The retrospective study was conducted from December 1, 2023, to April 1, 2024, at the Department of Histopathology, Dow Diagnostic Research and Reference Laboratory, Dow University of Health Sciences, Karachi, and comprised diagnostic reports of histopathology along with haematoxylin and eosin slides of patients diagnosed with oral squamous cell carcinoma and oesophageal squamous cell carcinoma from June 1, 2022, to June 1, 2023. Data ws compared to explore the association of perineural and lymphovascular invasion with tumour stage and nodal metastasis. Data was analysed using SPSS 26.

    Of the 100 cases, 60(60%) had oral squamous cell carcinoma, with 41(68.3%) being males and 35(58.3%) being aged >40 years. There were 40(40%) cases with oesophageal squamous cell carcinoma, with 28(70.2%) being males and 27(68.4%) being aged >40 years. Among the oral cases, perineural invasion (p<0.001) and lymphovascular invasion (p=0.05) were significantly associated with nodal metastasis. Depth of invasion was significantly associated with both perineural (p=0.024) and lymphovascular (p=0.047) invasion. Tumour size was significantly associated with perineural invasion (p=0.05), but not with lymphovascular invasion (p=0.227). Among the oesophageal squamous cell carcinoma cases, a significant association was identified for tumour stage with perineural invasion (p=0.047) and lymphovascular invasion (p=0.006). Perineural invasion (p=0.002) and lymphovascular invasion (p<0.001) were significantly associated with nodal metastasis.

    Perineural and lymphovascular invasion showed potential as diagnostic and therapeutic targets for managing oral squamous cell carcinoma and oesophageal squamous cell carcinoma.
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    Advocacy
  • Development of tri-cistronic CLDN18.2 CAR-T cells incorporating PD-1/CD28 switch and cyclophilin A for enhanced solid tumor immunotherapy.
    3 weeks ago
    Chimeric antigen receptor (CAR)-T cell therapy holds significant potential for the treatment of solid tumors. However, immune suppression and tumor-specific barriers limit its application. Claudin 18.2 (CLDN18.2), a gastric lineage-specific tight junction protein highly expressed in gastric and pancreatic cancers, is a promising therapeutic target. In this study, we aimed to develop a next-generation tri-cistronic CLDN18.2-directed CAR-T cell platform that integrates a programmed cell death protein 1 (PD-1)/CD28 chimeric switch receptor with cyclophilin A (CypA). This platform sought to counteract PD-1-mediated immunosuppression and enhance T-cell activation and persistence. We generated CLDN18.2 CAR-T cells incorporating costimulatory inducible T-cell costimulator (ICOS) domains using lentiviral vector-based recombinant engineering. We further evaluated their cytokine release, cytotoxic activity, and safety profiles. In vitro, tri-cistronic CAR-T cells exhibited markedly increased interferon γ and tumor necrosis factor α secretion and enhanced cytotoxicity against CLDN18.2-positive gastric cancer cells compared with conventional CAR-T constructs. In vivo, these cells showed superior antitumor efficacy and sustained tumor regression without observable toxicity in xenograft gastric cancer models. Collectively, these findings demonstrate that the integration of PD-1/CD28 signaling and CypA within a tri-cistronic framework significantly reinforces CAR-T cell functionality and durability. This suggests strong clinical potential as a next-generation immunotherapy for solid tumors.
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  • The Stockholm Pilot study for Lung cancer Screening (Stockholm PLUS): feasibility of baseline low-dose CT lung cancer screening in a high-risk Swedish female population.
    3 weeks ago
    Low-dose CT screening of high-risk groups has been shown to reduce lung cancer mortality, and the European Council has therefore recommended that member states explore the feasibility and effectiveness of this approach. In this study, we evaluate the implementation of low-dose CT screening for lung cancer in a Swedish female population. Patient/material and methods: Women aged 54-74 years in the Southern Stockholm region were contacted via an electronic questionnaire. Individuals who met the same eligibility criteria as in the NELSON trial (a minimum smoking history of 15 pack-years) were invited. The screening consisted of a baseline low-dose computed tomography (LDCT) scan, with the option for a follow-up scan in cases with intermediate findings. Findings were managed in accordance with modified Fleischner Society guidelines.

    Between September 2022 and September 2024, 34,580 invitation letters were sent to randomly selected women aged 54-74 years 11,607 individuals (33.4%) completed the questionnaire, whereof 1,106 (10%) met the inclusion criteria. 990 (90%) individuals accepted the invitation and underwent a baseline low-dose CT scan. There were 152 intermediate and 55 positive scans at baseline, and additional eight positive scans at follow-up. Fifteen cases of Lung cancer were found, yielding a positive prediction value (PPV) of 24%. 87% of the lung cancers were in stage IA.

    Organized lung cancer screening in a Swedish female population proved feasible, demonstrating a good participation rate, and a cancer detection rate consistent with findings from other major screening trials.
    Cancer
    Chronic respiratory disease
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    Advocacy
  • Dormancy and Recurrence in Breast Cancer Bone Metastasis: From Mechanisms to Clinical Translation.
    3 weeks ago
    Breast cancer bone metastasis often involves a prolonged dormancy phase, during which disseminated tumor cells (DTCs) remain undetectable and resistant to conventional therapies, posing a significant risk for late recurrence. Understanding the underlying mechanisms of tumor dormancy and reactivation is crucial for developing effective clinical interventions. However, current clinical translation faces multiple challenges, including limitations in detecting dormant tumor cells, insufficient biomarkers for dormancy, and difficulties in targeted drug delivery. Recent advances in elucidating the mechanisms of dormancy-such as the establishment of the pre-metastatic niche, intercellular communication in the bone marrow microenvironment, and signaling pathways regulating dormancy and reactivation-have provided novel therapeutic targets. Based on these mechanistic insights, nanotechnology-based drug delivery systems have emerged as promising strategies to precisely target dormant breast cancer cells in bone marrow niches. In this review, we summarize the current understanding of dormancy mechanisms in breast cancer bone metastasis, discuss the barriers hindering clinical translation, and highlight how mechanism-driven nanotherapeutic strategies may offer new opportunities to prevent recurrence by targeting dormant tumor cells.
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  • Tumor-specific antibody cocktail treatment suppresses colorectal tumor growth in mice.
    3 weeks ago
    Colorectal cancer (CRC) remains a leading cause of cancer-related mortality, with advanced-stage disease frequently marked by treatment resistance and recurrence. Tumor heterogeneity, driven by the accumulation of somatic mutations, undermines the efficacy of conventional therapies and limits the long-term success of targeted agents. There is an urgent need for new therapeutic strategies that can exploit, rather than be constrained by, this heterogeneity.

    We developed a personalized immunotherapeutic pipeline in the syngeneic CT26 murine model of CRC. Briefly, whole exome sequencing identified mutated surface proteins (MSPs) unique to these cells. Of these MSPs, we selected 10 for the generation of MSP-specific polyclonal antibodies (pAbs). These pAbs were tested for specificity and peptide binding to peptides via ELISA, tumor tissue by immunofluorescence, and tumor cells by flow cytometry. Therapeutic efficacy was evaluated in vivo using CT26 tumor-bearing mice treated with the pAb cocktail alone or in combination with anti-PD-1 immune checkpoint blockade. To assess clinical relevance, we analyzed The Cancer Genome Atlas (TCGA) whole exome sequencing data from 100 human CRC patients for MSP prevalence and inter-patient variability.

    The 10-pAb oligoclonal antibody cocktail preparations exhibited additive, high-affinity, tumor-specific binding with minimal reactivity to healthy tissues. In vivo, this pAb cocktail significantly suppressed tumor growth and, when combined with PD-1 blockade, prolonged median survival to over 90 days in treated mice compared to less than 25 days in controls. Whole exome sequence data revealed that the majority of human CRC tumors harbored 10 or more MSPs, with minimal overlap between individuals, highlighting the feasibility and necessity of personalized antibody-based therapies.

    Our findings establish a proof-of-concept for individualized, mutation-guided antibody therapies, supporting further development of this approach to improve outcomes in patients with advanced CRC.
    Cancer
    Care/Management
  • Randomized controlled trial: Synergistic effect of three-ball mindfulness breathing rehabilitation training following pulmonary lobectomy for lung cancer.
    3 weeks ago
    To investigate the synergistic effect of three-ball mindfulness breathing rehabilitation training in the context of postoperative rehabilitation for patients undergoing pulmonary lobectomy for lung cancer.

    A total of 124 patients with lung cancer who underwent pulmonary lobectomy at the First Affiliated Hospital of Xiamen University from March 2024 to January 2025 were selected and randomly divided into two groups (n = 62 each) using a random number table. The control group received conventional pulmonary rehabilitation training, while the observation group received three-ball mindfulness breathing rehabilitation training on top of the conventional regimen. The intervention for both groups continued until one week after discharge, during which patients performed exercises independently. Recovery indicators (primary outcomes), postoperative complications, and scores for dyspnea (mMRC), exercise tolerance (6MWT), emotional status (DASS), and fatigue (Piper Fatigue Scale, PFS) (secondary outcomes) were compared between the two groups at admission, 1 day before surgery, 3 days after surgery, and 1 week after discharge.

    The observation group showed shorter durations of pulmonary rales, sputum retention, and hospital stay compared to the control group (P < 0.05). At postoperative day 3 and 1 week after discharge, the mMRC scores were lower and 6MWT was higher in the observation group than in the control group (P < 0.05). At 1 day before surgery, 3 days after surgery, and 1 week after discharge, the DASS and PFS scores in the observation group were lower than those in the control group (P < 0.05). The incidence of complications did not differ significantly between the two groups (9.68% vs 17.74%, P > 0.05).

    Three-ball mindfulness breathing rehabilitation training can alleviate fatigue and dyspnea in patients after pulmonary lobectomy for lung cancer, regulate psychological status, and enhance exercise tolerance. It has a synergistic effect when combined with conventional pulmonary rehabilitation training.
    Cancer
    Chronic respiratory disease
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    Education
  • Heterologous prime-boost immunization of AAV-based neoantigen cancer vaccine induces anti-tumor immunity to inhibit tumor growth and relapse.
    3 weeks ago
    Therapeutic cancer vaccines, which induce anti-tumor immunity by targeting specific antigens, constitute a promising approach to cancer therapy. Our previous work developed a novel engineered adenovirus-associated virus 2 (AAV2)-based tumor-specific (neoantigen) cancer vaccine to boost antitumor immunity in combination with radiotherapy, resulting in tumor regression and less distant metastasis. However, the therapeutic efficacy of constitutive vector-based vaccination may be limited by poor immunogenicity, pre-existing vector-specific immunity, and vaccine-induced vector-specific immunity. Here, we examined the combinational therapeutic efficacy of AAV-based cancer vaccine, local radiotherapy, and immune checkpoint blockade (ICB) in different poorly immunogenic cancer animal models. We found that administration with AAV-based neoantigen vaccine significantly increased the response to radiotherapy and ICB, and decreased the risk of distant metastasis. Furthermore, we evaluated a heterologous prime-boost immunization strategy using two optimized AAV serotype vaccines to amplify tumor-specific immunity to neoantigens. These optimized AAV2/AAV6 neoantigen vaccine displayed strong immunogenicity with potent induction of CD8+ T cells. As combined with local radiotherapy, the prime-boost vaccine-induced superior tumor clearance and survival compared with other groups. Remarkably, optimized AAV2/AAV6 vaccination promoted CD8+ T-cell infiltration in the tumors and elicited the enrichment of T-cell clones. Furthermore, exhausted T-cell marker expression was significantly decreased in the tumor-infiltrating CD8+ T cells. Taken together, these results highlight the synergistic potency of engineered AAV2/AAV6 vaccines combined with local radiotherapy for poorly immunogenic cancers.
    Cancer
    Care/Management
  • Testicular Cysts in Broilers: A Study on Chronic Sodium Toxicity and Pathogenic Synergies.
    3 weeks ago
    Testicular cysts in poultry are pathologic conditions with significant implications for reproductive health and flock performance. This study investigated the clinical, molecular, and pathologic impacts of chronic sodium toxicity and its interplay with infectious agents in broiler chickens. In a flock of 22,600 Ross broiler chickens, a severe mortality rate (88.3%) was reported after showing signs of disease such as reduced feed intake, diarrhea, and lethargy. At necropsy, hydropericardium and testicular cysts, with no evidence of ascites, were observed. Severe intestinal necrosis, renal lesions characteristic of membranoproliferative glomerulonephritis, and in the testes, atrophy with no epithelial germ cells or seminiferous tubules were observed during histopathologic examination. Analysis of the feed revealed high levels of sodium in the feed (0.64% in the starter feed and 0.65% in the finisher feed). PCR assays detected adenovirus DNA, with positive results on day 15 and negative results on day 35, while bacterial cultures identified Escherichia coli exhibiting multidrug resistance. Symptoms and mortality did not improve with antibiotic treatment. Although adenoviral DNA was detected, the histopathologic findings supported sodium toxicity as the primary causative factor. Histopathologic examination, alongside PCR assays, is crucial for achieving a comprehensive and accurate understanding of the underlying causes in such cases. These findings show that there can be an interaction between an imbalanced diet and pathogens in broilers and thus the need for accurate feed formulation and diagnostic approaches to manage multiple causes of disorders in poultry production systems.
    Cancer
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  • Long-term efficacy of ursodeoxycholic acid for the prevention of gallstone formation after gastrectomy in patients with gastric cancer: a randomized clinical trial.
    3 weeks ago
    The optimal long-term strategy for preventing post-gastrectomy gallstone formation in gastric cancer (GC) remains unclear. This study evaluated the sustained efficacy of a 12-month course of ursodeoxycholic acid (UDCA) after gastrectomy for GC.

    We conducted a randomized, double-blind, placebo-controlled clinical trial at 13 institutions in the Republic of Korea. Patients who underwent total, distal, or proximal gastrectomy for GC were randomized 1:1:1 to receive either 300 mg UDCA, 600 mg UDCA, or placebo daily for 12 months. The primary outcome was the incidence of gallstone formation at least 5 years post-gastrectomy. Secondary outcomes were biliary pain, gallstone complications, and cholecystectomy.

    A total of 431 participants (300 mg UDCA: n = 141; 600 mg UDCA: n = 150; placebo: n = 140) were analyzed. At 80 months post-gastrectomy, gallstone formation occurred in 10.00% of the 300 mg group, 12.83% of the 600 mg group, and 26.21% of the placebo group. UDCA significantly reduced the hazard of gallstone formation compared to placebo (hazard ratio: 0.33, 95% CI 0.18-0.63, P = 0.0014 for 300 mg; 0.43, 95% CI 0.25-0.75, P = 0.0064 for 600 mg). There were no significant differences among groups in the incidence of biliary pain, gallstone complications, or cholecystectomy.

    Twelve months of UDCA administration was associated with sustained reduction in gallstone formation for up to 80 months after gastrectomy in GC patients.
    Cancer
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