Anticancer research最新文献

Background/aim: Few studies have reported the effects of radiotherapy on hepatocellular carcinoma (HCC) arising in transplanted liver tissue, and its safety and efficacy remain unclear. Here, we report a case of carbon-ion radiotherapy (CIRT) for HCC arising in transplanted liver tissue.

Case report: The patient was a 51-year-old man with a performance status score of 0 at the time of HCC referral. He had undergone living-donor liver transplantation for cirrhosis caused by Wilson disease approximately 13 years prior to CIRT for HCC. One year and four months prior to CIRT, a 38 mm HCC mass was diagnosed using ultrasound, computed tomography, and magnetic resonance imaging. Due to the history of liver transplantation, the surgeon determined that surgery for HCC was a high-risk procedure; consequently, the patient underwent transcatheter arterial chemoembolization (TACE). However, the lesions gradually grew. One year and four months after TACE, the patient was diagnosed with recurrent HCC (48 mm; rT1bN0M0, r-stage IB) based on imaging alone. Surgical management was determined to be challenging, and TACE was not considered effective in this case. The patient's liver dysfunction, assessed using the Child-Pugh classification, was favorable at 6 points (class A). Therefore, the patient received CIRT at 60 Gy (RBE) in four fractions to reduce radiation-induced toxicity. No acute adverse events were observed. A grade 2 increase in γ-glutamyl transpeptidase was observed 24 months after CIRT, which returned to normal naturally. The HCC showed no recurrence at 4 years and 7 months after the final follow-up. Two months later, the patient died of leukemia without any signs of HCC recurrence.

Conclusion: This case indicated that CIRT is a safe treatment option for HCC arising from transplanted liver tissue.

Background/aim: Assessment of nutritional status plays an important role in treatment of patients with lung cancer. We conducted a real-world study to investigate the potential prognostic value of baseline body mass index (BMI) in patients with non-small-cell lung cancer (NSCLC) treated with immune checkpoint inhibitors (ICIs).

Patients and methods: We retrospectively analysed data from 154 patients with advanced NSCLC treated with ICIs in the first or second line. Patients were stratified into two groups: BMI <25 kg/m² and BMI ≥25 kg/m². We investigated the impact of BMI on overall survival (OS), progression-free survival (PFS), time to treatment failure (TTF), and objective response rate (ORR) across the overall population and within prespecified subgroups defined by BMI.

Results: Patients with BMI ≥25 kg/m² (n=88) had a significantly better ORR compared to those with BMI <25 kg/m² (n=66): 78.4% vs. 62.1%, p=0.03. There was no significant improvement in PFS, TTF or OS in the overall population. Subgroup analyses showed significant improvement in OS in favour of the BMI ≥25 kg/m² group in non-smokers, in the subgroup receiving first-line immunotherapy, and in the subgroup with high expression of programmed cell death ligand 1. There was significant improvement in ORR in favour of the BMI ≥25 kg/m² group in several subgroups. No significant improvements in PFS and TTF in subgroup analyses were observed.

Conclusion: Our real-world study suggests that BMI might potentially act as a predictor for ORR in patients with advanced NSCLC treated with ICIs and should be considered in treatment decision-making. Additionally, we also observed a positive trend in OS among this group of patients.

Background/aim: Positron emission tomography (PET) imaging with either [¹⁸F]fluorodeoxyglucose (FDG) or [¹¹C]methionine (MET) can identify glucose addiction (Warburg effect) and methionine addiction (Hoffman effect), respectively, of cancer. Combined MET-PET and FDG-PET imaging of tumors for glucose and methionine addiction has been rare, except for the brain. The present report is a case of endometrial cancer in which a lymph-node metastasis was identified solely by MET-PET, with the primary tumor identified by both MET-PET and FDG-PET demonstrating the potential utility of MET-PET as a complementary imaging modality to FDG-PET in the detection of gynecologic malignancies.

Case report: A 58-year-old woman was diagnosed with atypical endometrial hyperplasia (AEH) based on biopsy and histopathological examination. FDG-PET revealed abnormal uptake in the endometrium, leading to a diagnosis of endometrial cancer. Subsequently, MET-PET confirmed the primary tumor and additionally detected para-aortic lymph-node metastasis, which was not visible on FDG-PET. The present findings enabled more accurate staging and suggest metabolic heterogeneity between the primary tumor and its metastasis, with the primary lesion dependent on both glucose and methionine, and the metastatic lesion methionine-dependent only.

Conclusion: The present case report is the first to demonstrate that lymph-node metastasis of endometrial cancer was detected exclusively using MET-PET, with no uptake observed with FDG-PET. The present findings suggest the hypothesis that metastatic lesions may undergo a metabolic shift from the primary tumor, changing from addiction to both glucose and methionine in the primary tumor, to methionine addiction alone in the metastasis.

Background/aim: There have been several anecdotal case reports documenting marked palliative benefits following treatment of terminal patients suffering from a variety of different types of cancer with the single agent selective progesterone receptor modulator (SPRM) mifepristone including stage IV treatment refractory small cell lung cancer (SCLC) and stage IV non-small cell lung cancer (NSCLC). The proposed mechanism of action is to suppress the production of immunomodulatory proteins that are the result of activating membrane progesterone receptors (mPRs). Case reports showing efficacy of a given therapy show that this type of treatment can be effective but gives the reader no indication as to whether that therapy is effective in just some rare cases or if it can provide benefit to a majority of cases.

Case report: Although a randomized controlled trial or a multicentered large series would be ideal, we waited until all of the six cases of very advanced treatment refractory stage IV lung cancer that we treated (two with SCLC, four with NSCLC) either died or survived five years taking single agent oral mifepristone. The dosage was either 200 or 300 mg/day. A 66.7% good quality 5-year overall survival ensued with death generally from co-morbidities not the lung cancer itself.

Conclusion: The likelihood of this type of response occurring by chance is extremely low. It is hoped that this report will encourage oncologists, scientists, and clinicians to further investigate the use of SPRMs in a larger cohort of patients with stage IV lung cancer, and potentially in those with less advanced disease.

Background/aim: Pulmonary emphysema, a key component of chronic obstructive pulmonary disease, is closely linked to frailty and systemic inflammation. While its prognostic significance has been explored in lung cancer, its impact in gastrointestinal malignancies, including colorectal liver metastases (CRLM), remains unclear.

Patients and methods: This retrospective study included 107 patients who underwent hepatic resection for CRLM. Preoperative emphysema was assessed using the Goddard score on computed tomography, with a cutoff of ≥7 defining as pulmonary emphysema. Clinical outcomes, including disease-free survival (DFS) and cancer specific survival, were analyzed.

Results: Pulmonary emphysema was observed in 26 (24%) patients. Those with high Goddard score had significantly worse DFS (3-year: 12.9% vs. 40.9%, p<0.01) and cancer specific survival (5-year: 42.8% vs. 76.8%, p=0.02). Multivariate analysis confirmed high Goddard score as an independent predictor of poor DFS (HR=1.49, p<0.01) and cancer specific survival (HR=1.63, p=0.02).

Conclusion: Pulmonary emphysema, as measured by the Goddard score, is independently associated with unfavorable oncologic outcomes in CRLM.

Background/aim: Targeting tumor-associated macrophages (TAMs) represents a promising strategy for next-generation immunotherapy. This study investigates the underlying mechanisms of TAM repolarization from the pro-tumorigenic M2 phenotype to the anti-tumorigenic M1 phenotype induced by itraconazole (ITZ).

Materials and methods: M2 macrophages derived from THP-1 cells were used in all experiments, and ITZ was administered at a concentration of 10^-5 M. Morphological changes were monitored via time-lapse imaging. Single-cell RNA sequencing (scRNA-seq) and triple-color immunostaining for organelles, cholesterol, and the M1 marker interleukin (IL)-1β were performed with and without ITZ treatment. For inhibition studies, β-cyclodextrin polyrotaxane (βCD-PRX), a compound that removes cholesterol from lysosomes, was used. The effects were assessed by time-lapse imaging and western blot analysis of the M2 marker CD163.

Results: Following ITZ treatment, a subpopulation of M2 macrophages exhibited morphological changes, shedding dendrites and migrating, indicative of an M1-like phenotype. Additionally, intracellular lipid droplets enlarged and swelled. scRNA-seq analysis revealed that M2 macrophages with reduced lysosomal vesicle biogenesis transitioned to an M1-like phenotype and identified 1,142 significantly enriched pathways, including M1-related signaling activation and cholesterol metabolism and transport pathways. Immunofluorescence analysis confirmed that macrophages shifting toward an M1-like phenotype expressed IL-1β, with enlarged intracellular lipid droplets identified as cholesterol-containing lysosomes. Notably, M2 macrophages that had adopted an M1-like morphology in response to ITZ reverted to their original M2-like shape and exhibited increased CD163 expression following βCD-PRX treatment.

Conclusion: Inhibition of lysosomal cholesterol release by ITZ reprogrammed M2 macrophages into an M1-like phenotype, revealing a novel mechanism that may serve as a foundation for developing innovative TAM-targeted immunotherapies.

Background/aim: Primary effusion lymphoma (PEL) is a rare and aggressive form of non-Hodgkin lymphoma (NHL) with poor prognosis due to resistance to conventional chemotherapy. Andrographolide (AG), a diterpenoid lactone extracted from Andrographis paniculata, has shown anti-tumor activity in several malignancies, but its effects on PEL are unknown.

Materials and methods: PEL cell viability was assessed by MTT assay. Apoptosis was evaluated via Annexin V/PI staining and caspase activation. ROS generation was measured by DCFH-DA staining. Protein expression changes were analyzed by Western blotting. To determine the roles of ROS and caspases, cells were co-treated with a reactive oxygen species (ROS) scavenger N-acetyl cysteine (NAC) or the pan-caspase inhibitor Q-VD-OPh. AG's in vivo effects were tested in a xenograft mouse model.

Results: AG inhibited PEL cell proliferation in a dose- and time-dependent manner. Apoptosis was mediated via ROS production and caspase activation. STAT3 phosphorylation was suppressed in a ROS-dependent manner. In vivo, AG (500 mg/kg/day, oral gavage) significantly reduced tumor burden without observable toxicity.

Conclusion: AG exerts anti-tumor effects against PEL by inducing ROS-dependent apoptosis and suppressing STAT3 signaling. These findings suggest that AG may serve as a promising therapeutic agent for PEL.

Background/aim: Perineal hernia (PerH) is a rare but challenging complication following abdominoperineal resection (APR). While primary repairs using mesh are commonly performed, recurrent or intractable cases often require more robust reconstructive options. Among these, myocutaneous flap techniques have emerged as promising alternatives, particularly in anatomically complex or previously treated patients. However, there remains no standardized surgical approach, and the choice of procedure must be individualized according to the patient's background, prior interventions, and anticipated risk of recurrence.

Case report: A 76-year-old man developed a perineal hernia two months after undergoing APR for rectal cancer. The hernia recurred despite two separate laparoscopic mesh repairs, indicating the limitations of conventional approaches in this setting. Imaging revealed a significant perineal bulge containing the small intestine and bladder, without evidence of malignancy or local tumor recurrence. Considering the failure of previous mesh repairs and the likelihood of severe pelvic adhesions, a salvage procedure was performed using a vertical rectus abdominis myocutaneous (VRAM) flap via a combined abdominal and perineal approach. The flap, based on the deep inferior epigastric vessels, was transposed to fill the pelvic floor defect and reinforce the weakened perineal region. Postoperative recovery was uneventful, and the patient has remained free of recurrence for 38 months. This durable outcome underscores the utility of flap-based reconstruction for complex pelvic defects.

Conclusion: This case demonstrates that VRAM flap reconstruction can provide durable and safe repair for recurrent perineal hernia after APR. It should be considered a valuable salvage option when conventional mesh repairs fail.

Background/aim: The relationship between postoperative complications and prognosis after laparoscopic distal gastrectomy (LDG) for gastric cancer (GC) remains controversial. This study evaluated this association using propensity score-matched analysis.

Patients and methods: We analyzed data of 590 patients who underwent curative LDG for GC at five institutions between January 2018 and December 2024. Patients were categorized into non-complication and complication groups (non-CG and CG, respectively), with complications defined as Clavien-Dindo grade ≥II (CD ≥II). Minor complications were defined as CD grades I or II, and major complications were defined as CD grades ≥III. Propensity score matching (PSM) was performed using the following covariates: age, sex, body mass index, American Society of Anesthesiologists physical status, extent of lymph node dissection, reconstruction method, Japanese Classification of Gastric Carcinoma stage, neoadjuvant chemotherapy, and adjuvant chemotherapy. Survival curves were compared using the log-rank test, and multivariate analysis was performed using the Cox proportional hazard models.

Results: Overall incidence of postoperative complications (CD ≥II) was 14.9% (88/590 patients). After the PSM (85 pairs), the CG group had a significantly longer postoperative hospital stay than the non-CG group [median (range), 18 (7-110) days vs. 9 (5-18) days; p<0.001]. Five-year overall survival (OS) rate was 90.7% in the non-CG group and 70.4% in the CG group (p=0.009), and 5-year relapse-free survival rate was 87.7% in the non-CG group and 70.9% in the CG group (p=0.027). Multivariable analysis identified age ≥80 years, postoperative complications (CD ≥II), and lymph node metastasis (pN) as independent prognostic factors for OS.

Conclusion: Reducing the incidence of postoperative complications (CD ≥II) may improve prognosis in patients with GC undergoing LDG, contributing to better treatment strategies for GC.

Background/aim: The AXL receptor tyrosine kinase (AXL) has been identified as a key driver of tumor progression and chemoresistance in non-small-cell lung cancer (NSCLC). However, the molecular mechanisms underlying AXL-mediated oncogenesis remain unclear. This study aimed to identify novel AXL downstream genes involved in NSCLC progression.

Materials and methods: Transcriptomic RNA sequencing and analysis were performed to identify genes downstream from AXL. Cellular proliferation was assessed using the CCK-8 assay. Glucose uptake was measured using a glucose uptake assay. mRNA expression levels of interferon-stimulated gene 15 (ISG15) were analyzed via reverse transcription-quantitative polymerase chain reaction, and the regulation of ISG15 transcription by AXL was evaluated through an ISG15 promoter activity assay.

Results: Transcriptomic RNA sequencing revealed ISG15 as a novel downstream target of AXL. ISG15 expression significantly enhanced cellular proliferation and glucose uptake in NSCLC cells. AXL transcriptionally upregulated ISG15 expression by modulating its 5'-promoter activity.

Conclusion: ISG15 is a newly identified target of AXL and may serve as a potential therapeutic target to overcome resistance in patients with NSCLC receiving AXL-targeted therapies.