Anticancer research最新文献

Background/aim: This study evaluated the diagnostic accuracy (DA) for colorectal adenomas (CRA), screened by fecal immunochemical test (FIT), using five artificial intelligence (AI) models: logistic regression (LR), support vector machine (SVM), neural network (NN), random forest (RF), and gradient boosting machine (GBM). These models were tested together with clinical features categorized as low-risk (lowR) and high-risk (highR).

Patients and methods: The colorectal neoplasia (CRN) screening cohort of 5,090 patients included 222 CRA patients and 264 non-CRA patients. Three consecutive fecal samples from each individual were analyzed by two fecal occult blood (FOB) assays. Five AI models including clinical features of CRN patients and CV test results were used to test the DA for CRA measured by receiving operating characteristic (ROC) curves.

Results: In conventional ROC analysis, the area under the curve (AUC) values for different AI models ranged from 0.659 and 0.691 (for AIs with LR and SVM), while the highest AUC values were reached by NN, RF, and GBM models (0.809, 0.840, and 0.858, respectively). In the hierarchical summary ROC (HSROC) analysis, the AUC values were as follows: i) with lowR variables, AUC=0.508; ii) with highR variables, AUC=0.566 and iii) with all AI models, AUC= 0.789. The differences in AUC values were: between i) and ii) p=0.008; between i) and iii) p<0.0001 and between ii) and iii) p<0.0001.

Conclusion: In detection of CRA, the AI models proved to be superior to the diagnostic features without AI. This is the first study to report that DA in the diagnosis of CRA can be enhanced by AI models that include clinical data of the patients and results of FIT test.

Background/aim: The CD155/TIGIT axis has recently emerged as a promising immunotherapeutic target in several malignancies. However, its prognostic relevance within the tumor microenvironment (TME) in patients with locally advanced rectal cancer (LARC) who have received neo-adjuvant chemoradiotherapy (neoCRT) remains unclarified.

Materials and methods: The levels of tumor CD155 and TIGIT⁺ T cells in pair-matched pre-neoCRT biopsies and post-neoCRT surgical tissues were evaluated in 110 LARC tissues using immunohistochemistry. The relationship between CD155, TIGIT⁺ T cells, and other clinicopathological parameters was analyzed.

Results: The level of tumor CD155 was significantly increased in the post-neoCRT surgical tissues, compared to pre-neoCRT biopsies (p=0.0491). Moreover, tumor CD155 expression correlated with increased risk of local recurrence (p=0.016) and the infiltration of CD3⁺ T cells in the post-neoCRT surgical tissues (p=0.026). Patients with high tumor CD155 were significantly associated with worsen 10-year disease-free survival (DFS), suggesting the prognostic value of tumor CD155 on DFS in LARC patients who received neoCRT treatment. However, no significant association was observed between TIGIT⁺ T cells and DFS in these patients.

Conclusion: Tumor CD155 may play a pivotal role in the response to neoCRT treatment through alternative immunological mechanisms and could become a novel immunotherapeutic target for LARC patients.

Background/aim: The five members of the mammalian muscarinic acetylcholine receptor family are encoded by the cholinergic receptor, muscarinic, 1-5 (CHRM1-5) genes. CHRM genes are incriminated in formation of various cancer types, but their roles in head and neck squamous cell carcinoma (HNSCC) are improperly understood. Aberrant epigenetic modifications of specific tumor-suppressor genes and oncogenes are known to promote cancer development. We aimed to analyze the connection between methylation of CHRM genes and HNSCC recurrence, with specific reference to human papillomavirus (HPV)-positive oropharyngeal carcinoma.

Materials and methods: We investigated the methylation state of CHRM1-CHRM5 genes expressed in 305 samples of primary HNSCCs by quantitative methylation-specific polymerase chain reaction. We explored associations between methylation of these genes and the clinicopathological characteristics of HNSCC (location of the tumor as well as recurrence) Results: We found 1.08±0.94 methylated genes per sample (range=0-5), with promoters of CHRM1-5 genes methylated in 85.9%, 47.5%, 10.2%, 17.7%, and 19.3%, respectively, of the evaluated samples. Methylation levels of CHRM2 were significantly raised in HNSCC samples compared to corresponding normal tissues (p<0.001). Although there was no significance of tumor location, analysis by Kaplan-Meier estimate and multivariate Cox proportional hazard methods showed that methylated CHRM2 was significantly associated with increased recurrence of HNSCC with HPV-positive oropharyngeal cancer.

Conclusion: CHRM methylation status is associated with HNSCC pathogenesis.

Background/aim: Kisspeptin has multifaceted roles in both normal and pathological conditions. Although lung cancer is a leading cause of cancer worldwide, the role of kisspeptin in lung cancer remains poorly understood. Thus, this study aimed to investigate the effects of kisspeptin on lung cancer.

Materials and methods: Mouse LLC cells were used to examine kisspeptin's effect on cell growth and death. Analyses for apoptosis, cell cycle, and senescence were conducted by flow cytometry, western blots, and immunocytochemistry. An in vivo tumor growth assay was conducted to confirm the effect of kisspeptin on LLC cells.

Results: Kisspeptin reduced LLC cell viability and growth rate. Consistently, kisspeptin arrested LLC cells at G₀/G₁ phase by altering protein levels involved in the cell cycle with no effect on apoptotic cell death. Furthermore, kisspeptin induced senescence of LLC cells. Kisspeptin increased intracellular ROS levels and altered p38 MAPK, AKT, and NF-[Formula: see text]B signaling. Moreover, the p38 MAPK inhibitor SB203580 negated the effects of kisspeptin on cell viability and senescence by blocking kisspeptin-induced phosphorylation of p38 MAPK. In addition, when administered intraperitoneally twice a week to male C57BL/6 mice bearing LLC cells, kisspeptin slowed syngeneic tumor growth without affecting body weight.

Conclusion: Kisspeptin represses mouse lung cancer growth by inducing p38 MAPK-mediated cellular senescence.

Background/aim: Solar ultraviolet radiation represents the most important environmental risk factor for skin cancer. However, vitamin D synthesis from sun exposure has been reported to exert anti-carcinogenic effects on melanocytes in vitro. This justifies the ongoing debate whether vitamin D status can be considered a risk and prognostic for primary cutaneous malignant melanoma. The aim of this study was to assess the relevance of the vitamin D status for melanoma risk and prognosis.

Materials and methods: A systematic review and meta-analyses were conducted using Medline (via PubMed) and ISI (Web of Science).

Results: Nine meta-analyses were conducted to assess the association between vitamin D status and melanoma risk, as well as prognosis (Breslow thickness, mitotic rate, tumor stage, and ulceration status). Patients with melanoma had significantly lower mean 25(OH)D levels compared to healthy controls, and there was a non-significant trend toward an increased melanoma risk in patients with vitamin D deficiency (≤20 vs. >20 ng/ml). Subgroup analyses of Southern European studies showed significant results. Low serum levels were significantly associated with greater Breslow thickness, the presence of mitoses, and ulcerated primary tumors, but not with higher tumor stage. We observed significantly increased risks for thicker tumors, mitotic tumors, and higher tumor stages in vitamin D-deficient patients.

Conclusion: This study demonstrates an association between low vitamin D status and both increased melanoma risk and worsened prognosis, further contributing to the growing body of evidence supporting the tumor-protective role of vitamin D.

Background/aim: Scapular osteosarcoma is a rare malignancy, and the understanding of its optimal treatment strategies and long-term outcomes remains limited. The purpose of the current study was to evaluate our institutional experience.

Patients and methods: We reviewed 14 patients (8 females, 5 males; mean age 44±17 years) treated for scapular osteosarcoma from 1985 to 2022. Tumors were confirmed histologically and treated with a multidisciplinary approach, including chemotherapy and surgery with a median follow-up of 10 years.

Results: Surgical complications occurred in eight patients, leading to repeat procedures in four. Complications were associated with the use of implants or allografts (p<0.01). Mean shoulder forward elevation and external rotation at follow-up were 42±61° and 12±16°, with a mean MSTS93 score of 61±19%. The 10-year disease-specific survival rates was 76%. Local recurrence was associated with worse survival (HR=13.19, p=0.04).

Conclusion: Scapular osteosarcoma is rare, and with multidisciplinary management, local control is essential to patient survival.

Background/aim: Lipoprotein(a) (Lp(a)) is a complex protein involved in the transport of insoluble lipids in plasma. Its expression is predominantly genetically determined, with 70% to over 90% influenced by the number of Kringle IV type 2 domains. This study investigated the association between preoperative serum Lp(a) level and development of post-pancreatectomy nonalcoholic fatty liver disease (NAFLD) in patients who underwent pancreatectomy.

Patients and methods: Serum Lp(a) level was measured preoperatively and retrospectively evaluated together with other known risk factors for NAFLD, which was defined using a computed tomography-based Hounsfield unit (HU) value for liver parenchyma below 40 HU at the anteroposterior midpoint.

Results: NAFLD developed after pancreatectomy in 40 patients (17.5%) in the high Lp(a)-group, which was significantly lower compared to the 30 patients (53%) in the low Lp(a)-group (p=0.01). There were no other significant background factors related to preoperative Lp (a) level. Multivariate analysis indicated that low Lp(a) level is an independent risk factor for postoperative NAFLD, as well as pancreatic head resection, a small residual pancreatic volume, poor intake of pancrelipase, and postoperative diarrhea.

Conclusion: NAFLD after pancreatectomy could be predicted preoperatively to a certain extent by examining serum Lp(a) level.

Background/aim: Colorectal cancer (CRC) has the third-highest incidence among human cancers. Advancements in chemotherapy and targeted therapy have improved the treatment outcomes for patients with CRC. However, the management of patients with unresectable metastatic CRC (mCRC) continues to be a significant challenge for clinicians worldwide, particularly for those with microsatellite stability (MSS) and the BRAF V600E mutation, as they are associated with the poorest prognosis.

Case reports: The present study describes two patients with unresectable MSS, BRAF V600E-mutated stage IV metastatic CRC using a biweekly alternating regimen of irinotecan and oxaliplatin combined with capecitabine and bevacizumab. Case 1 stabilized after alternating treatment, whereas Case 2 progressed after alternating treatment, with progression-free survival (PFS) of 20+ and 24.5 months, respectively. Circulating levels of carcinoemryonic antigen (CEA) dropped to near normal in both cases. A partial response (PR) was determined for both cases.

Conclusion: The two cases suggest that an alternating chemotherapy regimen of oxaliplatin and irinotecan, combined with capecitabine and bevacizumab is effective in the treatment of MSS, BRAF V600E-mutated stage IV metastatic CRC. The progression-free survival was significantly prolonged (both exceeding 20 months) compared to the first-line standard chemotherapy regimen for this disease. With a good balance between toxicity and efficacy, this alternating chemotherapy regimen can be considered as a potential first-line option for microsatellite-stable metastatic colon cancer.

Background/aim: The efficacy of preoperative chemoradiotherapy (CRT) in lower rectal cancer is determined by its effects on the primary tumor. However, the effects on the mesorectum have not been investigated. Furthermore, edema in the dissection planes is frequently observed after postoperative CRT. Herein, we aimed to evaluate the changes in mesorectal computed tomography (CT) values (CTVs) before and after CRT and its relationship with treatment efficacy.

Patients and methods: We retrospectively examined 46 patients with lower rectal cancer who had undergone preoperative long-course CRT before radical surgery. The CTVs were measured at four predetermined points within the mesorectum on the coronal and sagittal sections. The difference in the average CTVs before and after CRT (ΔCTV) was recorded for each patient. Associations between the ΔCTV and clinicopathological factors were investigated via univariate and multivariate analyses. Tumor regression grade (TRG) was divided into "poor response" (TRG 1a/1b) and "good response" (TRG 2/3) according to the Japanese Classification of Colorectal Carcinoma.

Results: The mesorectal CTVs increased after CRT in 28 patients and decreased in 18 patients. The ΔCTV was higher in small tumors (p=0.007), ypT0-2 stage (p=0.01), and good TRG response (p=0.002). Multivariate analysis demonstrated an independent association between the increase in ΔCTV and good TRG response (p=0.050) or earlier ypT stage (p=0.029).

Conclusion: The ΔCTV, which varied among patients with lower rectal cancer, was associated with ypT stage and TRG. ΔCTV may be useful in predicting the tumor response to CRT.