Anticancer research最新文献

Background/aim: Predicting lymph node metastasis (LNM) in early gastric cancer (EGC) is crucial for making treatment decisions. This study aimed to confirm risk factors for LNM and identify novel auxiliary biomarkers for predicting LNM in EGC.

Patients and methods: We established a training set, comprising 63 patients with LNM-EGC and 274 patients with non-LNM EGC, and a test set, comprising 19 patients with LNM-EGC and 146 non-LNM EGC. Immunohistochemistry for lymphangiogenic and related pathway components (VEGF-C, TGF-β1, SMAD2/3, VEGF-D, pSTAT3, E-cadherin, CD44, c-MET, YAP, and HER2), in situ hybridization for Epstein-Barr virus-encoded small RNAs, and multiplex PCR for microsatellite instability were conducted.

Results: In the training set, Lauren's diffuse/mixed classification, stromal desmoplasia, submucosal invasion ≥500 μm, lymphatic invasion, and high VEGF-C and SMAD2/3 expression were independent risk factors for LNM (p<0.05). A large tumor size, mixed histology, submucosal invasion, perineural invasion, and ulceration were determined as risk factors using univariate analysis (p<0.05). The tumor cutoff size for predicting LNM was 2.65 cm, based on a ROC analysis. The test set study verified that stromal desmoplasia, submucosal invasion, and high VEGF-C expression were independent risk factors for LNM (p<0.05). Moreover, mixed histology, lymphatic invasion, ulceration, and high SMAD 2/3 expression were identified as additional risk factors using univariate analysis (p<0.05).

Conclusion: Stromal desmoplasia, submucosal invasion, and high VEGF-C expression are potential biomarkers for LNM in EGC. VEGF-C expression might serve as an adjunct biomarker for predicting LNM on forceps-biopsy tissue at initial diagnosis.

Background/aim: Colorectal cancer (CRC) is one of the most widespread malignancies. One of the alternative therapeutic methods appears to be photodynamic therapy (PDT).

Materials and methods: This study investigated the efficiency of 5,10,15,20-tetrakis(4-sulfonatophenyl)porphyrin zinc (ZnTPPS₄) and chloro-aluminum phthalocyanine disulfonate (ClAlPcS₂) with two commercial photosensitive compounds 5,10,15,20-tetrakis(1-methylpyridinium-4-yl)porphyrin (TMPyP) and tetramethylthionine chloride (methylene blue, MB) in PDT for CRC in vitro. In addition to the study of the photodynamic effect on the viability of the colorectal carcinoma cell line HT29, cellular uptake, ROS production, and DNA damage were investigated.

Results: All photosensitizers showed good accumulation within HT29 cells, high efficiency in killing the cells, and a concentration-dependent increase in the production of ROS.

Conclusion: PDT using ZnTPPS₄ and ClAlPcS₂ may be effective in the treatment of CRC, achieving a similar photocytotoxic effect at much lower concentrations compared to MB.

Background/aim: Retinoic acid (RA) induces tumor cell differentiation in diseases like acute promyelocytic leukemia or high-risk neuroblastoma. However, the formation of resistant cells, which results from dysregulation of different signaling pathways, limits therapy success. The present study aimed to characterize basic regulatory processes induced by the application of RA in human neuroblastoma cells, to identify therapeutic targets independent of the often amplified oncogene MYCN.

Materials and methods: In MYCN-amplified Kelly and MYCN non-amplified SH-SY5Y cells, different assays were employed to quantify the viability and cytotoxicity, while RA-mediated expression changes were examined using genome-wide gene expression analysis followed by quantitative PCR. Enzyme-linked immunoabsorbent assays (ELISA) and western blots were used to determine the levels or activation of the examined proteins.

Results: In Kelly cells, treatment with 5 μM RA for 3 days significantly reduced the cell number due to attenuated proliferation, while SH-SY5Y cells were less responsive. An up-regulation of the RA-metabolizing enzymes CYP26A1 and CYP26B1 was observed in both cell lines, and co-treatment with the selective CYP26 inhibitor talarozole markedly decreased cell viability. When RA and ketoconazole, which inhibits CYP26 as well as RA-degrading CYP3A enzymes, were co-administered, not only cell survival was impaired in both cell lines, but also the release of hepatocyte growth factor (HGF). Accordingly, co-application of the c-Met inhibitor tepotinib and RA or ketoconazole substantially decreased cell viability.

Conclusion: Independent of MYCN amplification, inhibitors of RA metabolism or HGF signaling might prevent the emergence of RA-resistant neuroblastoma cells when co-applied with RA.

Background/aim: Non-small cell lung cancer is known for its rapid growth and immune evasion, demanding effective therapies targeting both tumor cells and the microenvironment. Magnolol has shown promising anti-tumor effects in various cancers.

Materials and methods: CL1-5-F4-bearing mice were divided into control, 40 mg/kg, and 60 mg/kg magnolol groups, once tumors reached 100 mm³ Tumor growth and body weight were monitored biweekly, and after 13 days, mice were euthanized for tumor and organ collection for subsequent staining. Histopathology and serum biochemistry assessed organ toxicity.

Results: Magnolol dose-dependently suppressed NSCLC progression, with no pathology alterations observed in normal organs. Magnolol-induced apoptosis and cell cycle arrest, evidenced by increased cleaved caspase-3 and decreased cyclin D1/CDK4 levels. It also down-regulated VEGF, FOXP3, and IDO-1 in tumors, implicating tumor microenvironment modulation.

Conclusion: Magnolol exhibits significant antitumor effects in NSCLC by inducing apoptosis, inhibiting proliferation, and modulating the tumor microenvironment. These results support further investigation of magnolol as a therapeutic adjuvant to enhance NSCLC treatment outcomes.

Background/aim: Patients with synchronous pancreatic ductal adenocarcinoma (PDAC) and nasopharyngeal carcinoma (NPC) have not been previously reported in the English literature. We present such a unique case with both PDAC and NPC.

Case report: A 72-year-old Asian-American female with a past medical history of primary biliary cholangitis presented with abdominal pain. Initial computer tomography (CT) scans demonstrated a 13 cm solid and cystic mass in the pancreatic body and tail with no mass identified in her liver. A biopsy of the pancreatic mass revealed pancreatic duct adenocarcinoma. Further evaluation with a positron emission tomography (PET) scan revealed a hypermetabolic mass (SUVmax10) in the nasopharynx. Subsequent biopsy results were consistent with nasopharyngeal carcinoma. Genetic counseling and next-generation sequencing (NGS) on her peripheral blood DNA were performed, identifying a pathogenic mutation of ATM c.8545C>T (p.Arg2849*). The patient was treated with gemcitabine-abraxane chemotherapy and FOLFIRINOX (fluorouracil, oxaliplatin, leucovorin and irinotecan) for her PDAC, while radiation therapy was proposed for her NPC. Ultimately, due to the progression of the malignancies, she entered hospice care and passed eight months after the diagnosis of PDAC.

Conclusion: To the best of our knowledge, this is the first documented case of synchronous PDAC and NPC in a patient with novel associated pathogenic ATM c.8545C>T (p.Arg2849*) mutation and poor prognosis. More similar case reports are needed to further characterize this entity.

Background/aim: Methotrexate (MTX) resistance in osteosarcoma results in a very poor patient prognosis. We previously reported that super MTX-resistant osteosarcoma (143B-MTX^SR) cells, selected from parental 143B osteosarcoma (143B-P) cells by culturing them with increasing concentrations of MTX, exhibited reduced malignancy, despite the over-expression of oncogenes. The present study explored the mechanism of reduced malignancy in the super MTX-resistant osteosarcoma cells.

Materials and methods: Previously selected 143B-MTX^SR cells which are 5,500 times more MTX resistant than parental cells, were used for this study. The status of methylated histone H3K9me3 and H3K27me3 marks was examined with western immunoblotting and compared between 143B-MTX^SR and parental 143B-P cells.

Results: Histone H3K9me3 and H3K27me3 marks were over-expressed in 143B-MTX^SR compared to 143B-P (p<0.05, p<0.01, respectively).

Conclusion: Over-expression of histone H3K9me3 and H3K27me3 marks may be related to super-MTX resistance and to the loss of malignancy of super MTX-resistant osteosarcoma cells due to the fundamental relationship of methylation and cancer.

Background/aim: This study compared the initial outcomes of gas-insufflation one-step single-port transaxillary (GOSTA) robotic thyroidectomy with traditional open thyroidectomy for thyroid cancer at a single institution.

Patients and methods: A retrospective analysis was conducted on 77 patients who underwent thyroidectomy for differentiated thyroid cancer from January to June 2024. Exclusion criteria included benign nodules, Graves' disease, and previous thyroid surgeries. Two surgeons performed the procedures, with one having no prior robotic surgery experience.

Results: Of the 77 patients, 48 underwent open thyroidectomy and 29 underwent GOSTA thyroidectomy. The GOSTA group had a significantly lower mean age (40.1 vs. 47.6 years, p=0.002) and a higher proportion of female patients (p=0.040). The open group patients had more harvested lymph nodes than the GOSTA group patients (7.9 vs. 2.4, p<0.001). The GOSTA group patients had longer operation time (156.4 vs. 80.6 min, p<0.001), and had extended hospital stay than the open group patients (5.9 vs. 3.4 days, p<0.001). Complication rates were similar between the groups.

Conclusion: GOSTA robotic thyroidectomy provides comparable safety and effectiveness to open thyroidectomy, with improved cosmetic outcomes despite longer operation times and hospital stays. This technique is feasible for surgeons without prior robotic experience, offering a viable alternative for patients prioritizing cosmetic results.

Background/aim: Many glioma patients struggle to return to work after surgery because of higher brain dysfunction. Although the right frontal lobe has historically been considered functionally silent, reports of performing awake surgery to evaluate higher brain functions in patients with tumors in this area have increased. We present two cases of patients who underwent awake surgery for malignant glioma in the right frontal lobe to preserve emotional recognition and facilitate an early return to work.

Case report: Case 1 was a 48-year-old right-handed woman employed as a nursery school teacher and case 2 was a 21-year-old right-handed man employed in sales. Both had contrast-enhancing right frontal lobe tumors exhibiting high signal intensity on fluid attenuated inversion recovery imaging and underwent awake surgery. During the operation, cortical mapping was performed using the Reading the Mind in the Eyes, calculation, and motor tasks. Resection of sites involved in motor and emotional recognition functions was avoided. In case 1, all regions of high signal intensity were completely resected; in case 2, all regions exhibiting enhancement were resected. Both patients were discharged home without neurological deficits and returned to work within 21 days after surgery.

Conclusion: It may be important to focus not only on overall survival and progression-free survival in glioma patients, but also on factors associated with life satisfaction, such as time to return to work after surgery and time until work becomes difficult. Awake surgery aimed at preserving higher brain functions is useful and may also improve life satisfaction.

Background/aim: As of 2024, anal cancer (AC) has been steadily increasing worldwide but, due to insufficient evidence, anal cancer screening (ACS) has yet to be standardized. Furthermore, most high-risk people in the world have no help paying for it. Therefore, our primary endpoint was to assess the best screening method for these subjects through a provision that was free of charge (all costs were covered by the Italian public health service). Awareness-raising campaign, determination of risk factors, education on anal self-examination, and sampling (ASS) were secondary objectives.

Patients and methods: Screening was on a voluntary basis. Engaging in receptive anal intercourse and having a history of cervical dysplasia were the main inclusion criteria. Level 1 ACS tools included digital ano-rectal examination, anoscopy, anal Pap, and anal human papillomavirus (HPV) DNA test (both through self- and proctologist- sampling); high-resolution anoscopy (HRA) with (HRAB) or without biopsy comprised level 2 screening. High-risk people were enrolled until the available funds were exhausted.

Results: Fifty high-risk people (40 men who had sex with men -MSM-, 9 women, and 1 heterosexual man) were enrolled. AC was found in one HIV-seropositive MSM, high-grade squamous intraepithelial lesion in 10 (20%) MSM, low-grade squamous intraepithelial lesion LSIL in 13 cases (12 MSM and 1 woman). The combination of HRAB and Pap smear screening achieved the highest values for sensitivity, specificity, and accuracy. ASS HPV DNA test provided excellent results comparable to clinician retrieval. Overweight and college education were identified as independent factors for the risk of and prevention of AC, respectively.

Conclusion: A free ACS not only appears justified but also recommended to people screened for AC. Excess weight represents a further risk for this population.

Background/aim: Although perioperative chemotherapy has improved patient survival, sarcopenia may occur during chemotherapy owing to decreased food intake and physical strength. However, reports on the occurrence of sarcopenia and changes in body composition in patients with pancreatic cancer during neoadjuvant chemotherapy are scarce. This study aimed to determine the effect of changes in skeletal muscle mass during neoadjuvant chemotherapy on the S-1 adjuvant chemotherapy clinical course in patients who underwent perioperative chemotherapy and surgical resection.

Patients and methods: We retrospectively enrolled 159 patients with pancreatic cancer who underwent neoadjuvant chemotherapy and surgical resection, followed by S-1 adjuvant chemotherapy. We evaluated changes in skeletal muscle mass during neoadjuvant chemotherapy using abdominal computed tomography and the SliceOmatic software. The association between the rate of change in skeletal muscle mass index (Δ%SMI) during neoadjuvant chemotherapy and the continuation of S-1 adjuvant chemotherapy was investigated.

Results: Eighty-eight (55.3%) patients lost skeletal muscle mass (Δ%SMI <0) during neoadjuvant chemotherapy with a significantly low S-1 adjuvant completion rate (p=0.02). Δ%SMI <0 was an independent risk factor for the continuation of S-1 adjuvant chemotherapy (hazard ratio=1.924, 95% confidence interval=1.002-3.695, p=0.049). Moreover, the lower the Δ%SMI, the lower the S-1 continuation rate (p=0.022).

Conclusion: Loss of skeletal muscle mass during neoadjuvant chemotherapy for pancreatic cancer affected the continuation of S-1 adjuvant chemotherapy after pancreatic resection. Therefore, ameliorating loss of skeletal muscle mass during neoadjuvant chemotherapy should be carefully considered to improve the continuation rate of adjuvant chemotherapy and the survival of patients with pancreatic cancer.