Anticancer research最新文献

Background/aim: Sentinel lymph node biopsy (SLNB) has become the standard procedure for axillary staging in clinically node-negative breast cancer. Traditionally, axillary lymph node dissection (ALND) has been performed when intraoperative pathological assessment revealed sentinel lymph node (SLN) metastasis. However, growing evidence suggests that postoperative radiotherapy and systemic therapy may safely replace ALND in selected patients, challenging the clinical necessity of intraoperative SLNB assessment.

Patients and methods: We retrospectively reviewed 540 patients with stage I-III primary breast cancer who underwent curative surgery and SLNB without intraoperative pathological evaluation between January 2018 and December 2021. Clinicopathological characteristics, adjuvant treatment strategies, and survival outcomes were analyzed, with a focus on patients with SLN metastases.

Results: SLN metastases were identified in 87 patients. Postoperative management consisted of ALND (n=19), axillary radiotherapy (n=39), systemic therapy alone (n=28), or no further treatment (n=1). Patients undergoing ALND showed a significantly higher recurrence rate compared with other treatment groups (p=0.028, log-rank), though ALND was more commonly performed in those with ≥3 positive SLNs or after mastectomy (p<0.001). In a high-risk subgroup of 31 patients not fulfilling ALND omission criteria, recurrence-free survival did not significantly differ between ALND and non-ALND groups (p=0.209, log-rank). Multivariate analysis confirmed that omission of ALND was not an independent prognostic factor for recurrence (hazard ratio=0.29; 95% confidence interval=0.03-2.39; p=0.248).

Conclusion: In the era of effective adjuvant radiotherapy and systemic therapy, the indications for omitting ALND may be further extended even to higher-risk patients. These results highlight the diminishing role of intraoperative pathological assessment of SLNB in contemporary breast cancer management.

Background/aim: Accurate preoperative localization is essential for successful breast-conserving surgery on non-palpable breast lesions. In recent years, Magseed has emerged as a non-wired localization approach with promising outcomes due to its flexibility and precision. This meta-analysis aimed to evaluate the efficacy and safety of Magseed localization on non-palpable breast lesions.

Materials and methods: Ovid MEDLINE, CINAHL, Ovid EMBASE, and The Cochrane Library were searched from inception to February 2025, following PRISMA guidelines. The pooled mean and proportions were analyzed using a random-effects model. The review was registered with PROSPERO (CRD420250654940).

Results: From 958 studies screened, 16 studies involving 2,117 patients and 2,176 Magseeds were included. The overall rate of positive margins was 7.6% [95% confidence interval (CI)=0.04, 0.11, I²=88%], and the re-excision rate was 8.2% (95%CI=0.05, 0.12, I²=87%). The overall complication rate was 0.6% (95%CI=0.001, 0.011, I²=7%). The success rate for Magseed placement was 99.3% (95%CI=0.987, 0.998, I²=1%), the migration-related failure was 0.6% (95%CI=0.001, 0.011, I²=0%), and the retrieval success rate was 99.6% (95%CI=0.992, 0.999, I²=0%). The mean operative time was 61.4 min (95%CI=55.9, 66.9, I²=98%).

Conclusion: Magseed appears to be a safe and effective technique for the preoperative localization of selected non-palpable breast lesions. Nonetheless, further studies based on breast density, size, and depth are required to investigate the feasibility of preoperative Magseed localization for patients with non-palpable breast lesions.

Background/aim: Limited evidence exists regarding the superiority of robotic surgeries (RS) over laparoscopic surgeries (LS) in right hemicolectomy (RHC) for right-sided colon cancer. This study aimed to clarify the safety and feasibility of RS in right-sided colon cancer.

Patients and methods: Patients who underwent RHC for right-sided colon cancer at a single institution between January 2021 and December 2023 were included. Patients with transverse colon cancer, those requiring emergency surgery, individuals with multiple malignancies, or those with non-adenocarcinoma histology were excluded. All procedures were performed using the inferior approach. Short-term outcomes, including operative time, estimated blood loss, postoperative complication rates, and length of hospital stay, were compared between the RS and LS groups.

Results: A total of 83 patients met the inclusion criteria. Among these, 57 underwent laparoscopic surgery, and 26 underwent robotic surgery. The RS group demonstrated significantly fewer postoperative complications [1 (4.1%) vs. 15 (30.6%), p=0.01] and a low postoperative ileus rate [0 (0%) vs. 5 (10.2%), p=0.04] compared with the LS group. Additionally, the RS group demonstrated a significantly shorter postoperative hospital stay [median 8 (range=7-36) days vs. 10 (7-56) days, p<0.0004].

Conclusion: RS for right-sided colon cancer reduced perioperative complications and shortened hospital stays, proving to be as effective as LS and demonstrating its safety and feasibility. However, robust evidence should be established through future large-scale, randomized controlled trials comparing RS and LS for right-sided colon cancer.

Background/aim: Reportedly, in laparoscopic surgeries for colorectal cancer, surgeries performed or supervised by Endoscopic Surgery Skills Qualification System (ESSQS)-certified surgeons yield favorable outcomes. However, the impact of ESSQS-certification on the prognosis of multivisceral resection (MVR) surgery remains unclear. The aim of this study was to examine the impact of MVR surgery performed by ESSQS-qualified surgeons on patient prognosis.

Patients and methods: We retrospectively reviewed 226 consecutive colorectal cancer patients who underwent MVR between 2016 and 2024. The patients were divided into two groups: surgery performed by ESSQS-certified surgeons (expert group, n=88) and those performed by ESSQS-uncertified surgeons (non-expert group, n=138). Propensity score matching for baseline patient and surgical characteristics identified 65 patients in each group. Groups were compared for clinicopathological and surgical features, and 5-year relapse-free survival (RFS), overall survival (OS) and local recurrence free survival (LRFS) were assessed using Kaplan Meier methods and log-rank tests.

Results: Before matching, the incidence of rectal cancer was higher (33.0% vs. 8.7%, p<0.001) and laparoscopic surgery was more often performed (89.8% vs. 79.7%, p=0.043) in the expert group. Five-year RFS (74.8% vs. 63.1%, p=0.056), OS (83.3% vs. 64.4%, p=0.062), and LRFS (3.5% vs. 11.4%, p=0.078) tended to be better in the expert group.

Conclusion: The results of this multicenter study indicated better short- and long-term outcomes of MVR performed by ESSQS-qualified surgeons.

Background/aim: THEMIS2, a protein that plays a role in immune regulation, has recently been identified as a key factor in breast cancer progression. This study aimed to identify novel oncogenic regulators in circulating tumor cells (CTCs) that contribute to breast cancer metastasis and chemoresistance, elucidating the regulatory axis involving THEMIS2, VEGFR2 and microRNAs (miRNAs), specifically miR-125b-5p.

Materials and methods: Using RNA-sequencing of breast cancer CTCs, THEMIS2 was identified as a significantly upregulated gene. miRNA target predictions and expression profiling in primary tumors and normal breast specimens were conducted to evaluate candidate regulators. Functional assays including sphere formation, migration, luciferase reporter activity, VEGFR phosphorylation analysis and in vivo tumor models were employed to investigate the roles of THEMIS2 and miR-125b-5p in metastasis and drug sensitivity.

Results: THEMIS2 was found upregulated in CTCs and breast cancer cell lines with metastatic potential. miR-125b-5p, but not miR-125a-5p, was significantly down-regulated in metastatic models and identified as a direct post-transcriptional suppressor of THEMIS2. THEMIS2 enhanced VEGFR2 phosphorylation and promoted metastatic traits and resistance to docetaxel and bevacizumab. miR-125b-5p suppressed metastasis and restored chemosensitivity by targeting 3'UTR of THEMIS2, an effect reversible with anti-miR-125b or ectopic THEMIS2 expression.

Conclusion: We unraveled a novel miR-125b-5p-THEMIS2-VEGFR2 signaling axis as a key modulator of breast cancer metastasis and chemoresistance. These findings provide mechanistic insight and suggest that miR-125b-5p or THEMIS2 may serve as therapeutic targets or prognostic biomarkers in aggressive breast cancers.

Background/aim: Aberrant glycosylation is recognized as a trait of tumorigenesis. Paucimannosidic glycoepitopes (PME), a class of small mannosidic N-linked glycans have recently been linked to pathophysiologic conditions such as cancer and infection. This study aimed to investigate whether paucimannosylation is present in ovarian cancer and to explore its prognostic relevance.

Patients and methods: We investigated the presence of PMEs in 176 patients with high-grade serous ovarian cancer using the research Mannitou antibody for immunohistochemistry. Immunohistochemical staining was assessed using eight different scoring systems and correlated with survival using the Kaplan-Meier method.

Results: Positive immunohistochemical staining of PMEs in immune cells was associated with improved 5-year disease-free survival (16.06% vs. 6.16%; p=0.032) and a trend toward improved 5-year overall survival (42.20% vs. 36.70%; p=0.052). Focal hot spot PME staining affecting more than 50% of tumor cells was associated with reduced 5-year overall survival (46.23% vs. 23.68%; p=0.029). Clinical factors such as tumor load, tumor distribution or FIGO-Stage showed no association with any PME staining pattern.

Conclusion: Paucimannosylation, indicated by the presence of PMEs, is present in both tumor and immune cells in high-grade serous ovarian cancer. The prognostic implication of PMEs seems to be cell type-dependent. While immune cell paucimannosylation was associated with improved survival, tumor cell paucimannosylation was associated with reduced survival.

Background/aim: Flavones are known as a prominent subclass within the flavonoid family and occupy an important part of the human diet. Their distinctive structure has been considered to show the activities and thus they represent a privileged scaffold in medicinal chemistry. Although we recently reported the systematic synthesis of polymethoxylated 3-styrylflavones, they did not show significant antiproliferative activity. Therefore, we designed and synthesized a series of 3-styrylflavones possessing a variously hydroxylated D-ring moiety due to investigating contribution of the hydroxyl groups to the antiproliferative activity.

Materials and methods: 3-Styrylflavones with a hydroxylated D-ring were systematically synthesized by the Wittig reaction between the various hydroxylated benzaldehyde derivatives and the 3-(bromomethyl)flavone derivatives prepared from 3-methylflavones, and their antiproliferative activity against HL60 was evaluated.

Results: Among the synthesized compounds, 2‴,5‴-dihydroxy-2',3',4'-trimethoxy-3-styrylflavone and 2‴,5‴-dihydroxy-3',4',5'-trimethoxy-3-styrylflavone (IC₅₀=16 μM) demonstrated the most significant antiproliferative activity.

Conclusion: The introduction of a hydroxyl group in 3-styryl substituent of 3-styrylflavone greatly increased the antiproliferative activity. Structure-activity relationship studies clearly indicated the importance of the hydroquinone structure as the D-ring moiety and suggested the possibility that the 3-styrylflavones possessing hydroquinone-type D-ring moiety act as "mitocan".

Background/aim: This study aimed to report clinical outcomes of spine stereotactic body radiation therapy (SBRT) using biaxially rotational dynamic radiation therapy (BROAD-RT), which is a novel non-coplanar volumetric-modulated arc therapy (VMAT) technique that does not require couch rotation or patient repositioning.

Patients and methods: We retrospectively analyzed 13 patients who received spine SBRT using BROAD-RT in a prospective feasibility study conducted between August 2020 and April 2022. The prescribed dose was 27 Gy in 3 fractions. Patient-specific dosimetric quality assurance (QA) using ArcCHECK was conducted.

Results: The median age of patients was 73 years old. Primary cancers involved the prostate (23.0%, N=3), lung (15.4%, N=2), breast (15.4%, N=2), liver (15.4%, N=2), thyroid (15.4%, N=2), malignant meningioma (7.7%, N=1), and synovial sarcoma (7.7%, N=1). Overall, 84.6% of patients (N=11) had oligo-metastatic disease at the time of SBRT. QA showed average (±standard deviation) passing rates of 96.4 ± 2.5%. The median follow-up period was 36.2 months. Local control (LC) and overall survival (OS) rates were 84.6 and 100% at one year, and 59.8 and 68.4% at three years, respectively. The cumulative incidence of grade ≥2 vertebral compression fracture (VCF) was 7.7 and 23.1% at one and three years, respectively. Other than VCF, no grade ≥3 toxicities or radiation-induced myelopathies were observed.

Conclusion: BROAD-RT enabled the easy application of non-coplanar VMAT in spine SBRT with marked accuracy. Treatment with 27 Gy in three fractions resulted in acceptable toxicity, although LC was relatively low. These findings highlight both the feasibility of BROAD-RT and the need for further investigation of dose and fractionation strategies.

Background/aim: This study aimed to evaluate whether the predictive performance of tumor control probability (TCP) by carbon ion radiotherapy (CIRT) could be improved by incorporating cancer type-specific carbon ion sensitivity data obtained from non-small cell lung cancer (NSCLC).

Materials and methods: A TCP model based on the linear-quadratic (LQ) formalism and fractionated irradiation was employed, with σ defined as an index of inter-tumor heterogeneity on radiosensitivity. The LQ model parameters α and β for NSCLC were obtained from 13 cell lines subjected to carbon ion irradiation under clinically relevant conditions, followed by clonogenic assays. The human salivary gland (HSG) cell line was used as a control. The α and β values were incorporated into the TCP model, and agreement with the clinical data (i.e., the local control rates for 48 NSCLCs treated with CIRT, as previously reported) was evaluated using the coefficient of determination (R²) derived from least-squares fitting.

Results: When σ was set to 0.20, the NSCLC-derived TCP curve showed better agreement with the clinical data than the HSG cell-derived TCP curve (R²: 0.72 vs. 0.53, respectively). Similarly, when σ was set to 0.15, the NSCLC-derived curve showed better agreement with the clinical data (R²: 0.56 vs. 0.38, respectively). Furthermore, when weighting factors of 1, 3, and 10 were applied to the two data points with TCP=1.0, the NSCLC-derived TCP curve showed consistently better agreement with the clinical data than the HSG cell-derived TCP curve (R²: 0.74 vs. 0.55, 0.78 vs. 0.63, and 0.79 vs. 0.65, respectively).

Conclusion: Incorporation of cancer type-specific carbon ion sensitivity data can improve the predictive performance of TCP modeling compared with the conventional HSG cell-based approach.

Background/aim: Osteosarcoma (OS) is refractory to immune checkpoint inhibitors targeting programmed cell death 1 (PD1)/PD ligand 1 (PD-L1) due to poor immune response. We previously developed telomerase-specific, replication-competent oncolytic adenoviruses non-armed OBP-301 and P53-armed OBP-702 that exert antitumor efficacy against human OS cells. Recently, we demonstrated that P53-armed OBP-702 induces more profound immunogenic cell death and antitumor immune response against human and murine OS cells than does non-armed OBP-301. In the present study, we assessed the combined efficacy of PD1 blockade and P53-armed OBP-702 against murine OS cells.

Materials and methods: Three murine OS cell lines (K7M2, NHOS, NHOS-LM4) were used to assess the cytopathic effect of non-armed OBP-301 and P53-armed OBP-702 by XTT assay. Virus-induced immunogenic cell death was assessed by analyzing the levels of extracellular adenosine triphosphate and high-mobility group box protein B1. The expression of PD-L1 and PD-L2 was analyzed by flow cytometry. The malignant potential of NHOS-LM4 cells was analyzed by a migration and invasion assay. An orthotopic NHOS-LM4 tumor model was used to evaluate the antitumor efficacy of combination therapy with P53-armed OBP-702 and anti-PD1.

Results: P53-armed OBP-702 exhibited antitumor potential for the induction of immunogenic cell death, apoptosis, autophagy, and PD-L1/2 upregulation in K7M2 and NHOS cells. NHOS-LM4 cells showed increased migratory and invasive ability compared to NHOS cells. P53-armed OBP-702 significantly suppressed the malignant potential of NHOS-LM4 cells. Combination dosing showed that P53-armed OBP-702 significantly promoted the antitumor effect of PD1 blockade against NHOS-LM4 tumors.

Conclusion: Our results suggest that P53-armed OBP-702 is a promising agent for improving the antitumor effect of PD1 blockade in treating invasive OS.