Anticancer research最新文献

Background/aim: Amrubicin is recognized as a second-line treatment for refractory small-cell lung cancer (SCLC) and is administered immediately after chemotherapy; however, it has not been evaluated in patients with recurrent SCLC following chemoradiotherapy (CRT). This study aimed to examine the activity and safety of amrubicin monotherapy in patients with relapsed SCLC previously treated with CRT.

Patients and methods: This retrospective study evaluated patients with relapsed SCLC who had been previously treated with CRT, followed by amrubicin monotherapy between April 2007 and June 2021. The clinical efficacy and toxicity were assessed.

Results: Overall, 30 patients (20 men and 10 women) were enrolled. The response rate was 50.0% [95% confidence interval (CI)=33.1-66.8%]. The median progression-free survival and overall survival from the first amrubicin treatment was 4.1 months (95%CI=2.3-6.0 months) and 13.5 months (95%CI=7.5-16.0 months), respectively. Grade ≥3 hematological adverse events occurred as follows: decreased white blood cells in 63.3% of patients, decreased neutrophil count in 70.0%, and febrile neutropenia in 10.0%. Grade 3 pneumonitis was observed in one patient. No treatment-related deaths occurred.

Conclusion: Amrubicin is both feasible and effective in patients with relapsed SCLC who were previously treated with CRT. The efficacy and toxicity of amrubicin in this study were consistent with those of previous reports, indicating that amrubicin retained its effectiveness post-CRT. Consequently, amrubicin following CRT may be the optimal chemotherapeutic choice for patients with relapsed limited-disease SCLC.

Background/aim: Brain metastases (BMs) are rare in lung squamous cell carcinoma (LUSC). Therefore, research on biomarkers or mechanisms that can be used to predict them is limited. To verify whether mRNA profiles can accurately predict BMs, we used a machine learning approach on 20 TNM-matched LUSC tissue samples.

Materials and methods: We conducted pathway and immunohistochemical analyses to investigate the underlying mechanisms of BM.

Results: A total of 15 mRNAs linked to BM were identified. The 15-mRNA signature was highly accurate in predicting BM, with an area under the curve and accuracy of 0.940 and 0.9, respectively. The pathway analysis revealed that immune-related pathways (leukocyte transendothelial migration, Fc gamma R-mediated phagocytosis, and natural killer cell-mediated cytotoxicity) were suppressed, suggesting that an immunosuppressive state may be involved in the development of BM. In the validation set confirmed by immunohistochemical staining, the BM group exhibited significantly lower levels of CD4+ T cells or CD8+ T cells than the group without BM. BM in patients with LUSC was associated with an immunosuppressive state.

Conclusion: Immunotherapy may be effective in preventing BM in patients with LUSC.

Background/aim: Hypoxia-inducible factor-1 alpha (HIF-1α) plays a key role in the cellular response to hypoxia, which plays a crucial role in the induction of abnormal angiogenesis and metastasis. Understanding the mechanism for the regulation of angiogenesis by HIF-1α-regulating miRNA will contribute to developing the strategy to prevent metastasis.

Materials and methods: We conducted a functional screening for HIF-1α-inhibiting miRNAs by evaluating the effects of miRNA mimics on HIF-1α expression and identified miR-5586-5p as an angiogenesis inhibitor through a mechanistic study. Angiogenic activity was assessed by tube formation assays using HUVEC cells exposed to conditioned media from miRNA-transfected breast cancer cells. In vivo activity of miR-5586-5p was examined through intratumoral injection of miRNA in orthotopic xenograft mice established by injecting MDA-MB-231 cells into the mammary fat pads of BALB/c nu/nu mice.

Results: The expression of the critical proangiogenic factors vascular endothelial growth factor A (VEGFA) and angiopoietin-like protein 4 (ANGPTL4) was inhibited by miR-5586-5p. Migration and tube formation of human umbilical vein endothelial cells were reduced in the conditioned medium prepared from miR-5586-5p-transfected cells. miR-5586-5p also suppressed the expression of heparin-binding EGF-like growth factor (HBEGF) and a disintegrin and metalloprotease 17 (ADAM17), which play a role in hypoxic signaling to induce the expression of VEGFA and ANGPTL4. HIF-1α, HBEGF, and ADAM17 were verified as the direct targets of miR-5586-5p responsible for the angiogenesis-suppressing function of miR-5586-5p. Expression levels of miR-5586-5p were lower in tumor tissues than in neighboring normal tissues of breast cancer patients. The expression of miR-5586-5p was inversely correlated to those of HIF-1α, HBEGF, ADAM17, VEGFA, and ANGPTL4. Angiogenesis and subsequent tumor growth were suppressed by intratumoral injection of miR-5586-5p in orthotopic MDA-MB-231 xenografts in mice.

Conclusion: A potent tumor-suppressive function of miR-5586-5p applicable for the development of a novel cancer treatment strategy is herein described.

Background/aim: Endocytoscopy (EC) enables real-time diagnosis at extremely high magnification. The aim of the present study was to assess the potential of EC for the prediction of biliary malignancy.

Patients and methods: In total, 23 surgically resected cases with biliary tract cancer (BTCA, n=6), pancreatic head cancer (PCA, n=13), and non-cancerous bile duct lesion (NCBL, n=4) were enrolled in the study. The extrahepatic bile duct mucosa of the resected materials was examined ex vivo using EC.

Results: In cases of BTCA and PCA with bile duct invasion, several independent findings were identified as predictors of cancerous areas using multivariate analysis. These include, extravasation [odds ratio (OR)=15.91; 95% confidence interval (CI)=2.05-123.46], absence of fine network (OR=6.16; 95%CI=1.88-20.19), vascular dilatation (OR=4.87; 95%CI=1.56-15.25) in direct view. Additional predictors observed under methylene blue staining include anisonucleosis (OR=27.77; 95%CI=6.85-112.56), absence of large glands (OR=27.77; 95%CI=6.85-112.56), obscured nuclei (OR=7.63; 95%CI=2.23-26.17), and absence of uniform glands and small/irregular glands (OR=6.18; 95%CI=2.25-16.98). There were no differences in EC findings of non-cancerous areas between BTCA/PCA and NCBL. EC score for predicting the cancerous area (ECS-CA) was established by summing the scores (regression coefficients) of the eight EC findings described above. In the receiver operating characteristic curve analysis, the area under the curve for predicting cancerous areas using the ECS-CA was 0.960 (optimal cut-off ECS-CA, 6.1; sensitivity 91.5%; specificity, 93.6%).

Conclusion: ECS-CA is valuable for assisting in the real-time diagnosis of biliary malignancy in vivo.

Background/aim: Combination therapy with immune checkpoint inhibitors has become the standard first-line treatment for metastatic renal cell carcinoma (mRCC), leading to changes in second-line treatment options, such as nivolumab or tyrosine kinase inhibitors (TKIs). However, very few studies have compared the efficacy of these drugs in patients with mRCC, particularly those with bone metastases (BM), which are associated with a poor prognosis. This study compared the efficacy of nivolumab and TKIs as second-line treatments for mRCC patients with BM and examined the microenvironments of primary tumors and BM lesions.

Patients and methods: This multi-institutional retrospective study included 87 mRCC patients with BM who received either nivolumab or TKIs as second-line treatments. We analyzed tumor-infiltrating immune cells expressing CD8 and CD20, along with PD-L1, HIF2α, c-MET, VEGFR2, and AXL, in primary tumors and BM sites using immunohistochemistry.

Results: This analysis indicated that poor-risk classification, as per the International Metastatic RCC Database Consortium criteria (p<0.01), and elevated serum alkaline phosphatase levels (p=0.031) were significantly associated with poor prognosis. No significant difference in overall survival was observed between patients receiving nivolumab and those receiving TKIs. However, the objective response rate of patients with BM lesions was significantly higher when receiving TKIs than when receiving nivolumab (p=0.014). Immunohistochemistry revealed significantly higher VEGFR2 expression in BM lesions than primary tumors.

Conclusion: TKIs could be a promising second-line treatment option for mRCC patients with bone-limited metastases.

Background/aim: Perioperative rehabilitation is effective in preventing postoperative complications and is associated with a shorter length of hospital stay after gastrectomy. However, its impact on short-term outcomes in patients without post-gastrectomy complications has not yet been clarified. This study aimed to evaluate the usefulness of perioperative rehabilitation beyond preventing postoperative complications.

Patients and methods: Of the 142 patients who underwent surgery for gastric cancer at our hospital between November 2017 and December 2022 and were treated according to the Enhanced Recovery After Surgery (ERAS) protocol during the perioperative period, 106 patients who were discharged without postoperative complications (with Clavien-Dindo classification < Grade 1) and did not undergo readmission within 30 days after surgery were included in the study. Perioperative rehabilitation was provided from August 2020. Patients were divided into the following two groups: Group A (with cancer rehabilitation; n=55) and Group B (without cancer rehabilitation; n=51), and their clinicopathological characteristics and short-term results were compared. Risk factor analysis was performed based on the number of days of postoperative hospitalization.

Results: The number of days of postoperative hospitalization in Group A (average 8.6 days) was significantly shorter than that in group B (average 9.9 days) (p=0.032). Multivariate analysis of postoperative hospital stay revealed that older age (p=0.003), female sex (p=0.043), heavy bleeding (p=0.026), and no rehabilitation (p=0.004) were independent risk factors.

Conclusion: Even in patients without postoperative complications, perioperative rehabilitation for gastric cancer could be effective in shortening the postoperative hospital stay.

Background/aim: Decreasing numbers of tonsillectomies (TE) and an increasing frequency of oropharyngeal squamous cell carcinoma (OPSCC) is a well-known finding in western societies. A retrospective cohort study was performed to investigate the association between a history of TE and the development of OPSCC.

Patients and methods: This study included all OPSCC patients who were treated between 2004 and 2023 at the Department of Otorhinolaryngology in University Medical Centre Ruppin Brandenburg in Germany. Digital patient charts were used to collect patient information.

Results: Of the 320 patients with OPSCC, 19 (5.9%) had a history of TE. In 63.2% of cases, the procedure was performed in childhood, and 36.8% in adulthood. Our results indicate significant differences in terms of tumor location between the patients with and without a history of TE (p=0.010). In patients without TE, OPSCC was localized in the tonsillar region (45%), in the base of the tongue (29%), and other regions (26%). In patients with a history of TE the frequency was 16%, 63%, and 21%, respectively. Age at initial diagnosis, initial tumor size, p16/HPV status, residual tumor, venous and lymphatic extracapsular extension, recurrence, and alcohol abuse significantly influenced overall survival without any difference between the two groups.

Conclusion: A history of TE is associated with a decreased risk of tumor localization in the tonsillar region, especially when TE was performed in adulthood. Additionally, in patients with OPSCC and a history of TE, the tumor is more frequently localized at the base of the tongue. A history of TE does not affect demographics, the outcomes of tumor parameters or the prognosis of our patients.

Background/aim: This study aimed to clarify the prognostic significance of splenic vein (SpV) invasion in patients with pancreatic cancer, which is not currently included in the anatomical resectability classification, compared with that of portal vein (PV) and/or superior mesenteric vein (SMV) invasion.

Patients and methods: A total of 188 patients with pancreatic cancer who underwent macroscopic radical pancreaticoduodenectomy (n=107) or distal pancreatectomy (n=79) were analyzed. The characteristics and prognosis of patient with SpV invasion were analyzed and compared with those of patients with PV/SMV invasion or without PV system invasion.

Results: Patients with SpV invasion had a more advanced tumor status, such as large tumor size and arterial invasion. Consequently, they included relatively more patients with microscopically residual tumors than those without PV system invasion. The prognosis of patients with SpV invasion was equivalent to that of patients with PV/SMV invasion (p=0.816) and significantly worse than that of the non-invasive group (p=0.015). SpV invasion was also an independent poor prognostic factor in multivariate analysis (p=0.042). Additionally, the prognosis of patients with SpV invasion was notably better when they underwent preoperative chemotherapy compared to those who did not (p=0.018). This finding represents a significant distinction from patients with PV/SMV invasion or those without PV system invasion.

Conclusion: Although SpV invasion is not classified as an anatomically unresectable/borderline-resectable factor, it is a significantly poor prognostic factor, similar to PV invasion. Additionally, patients with SpV invasion may benefit more from neoadjuvant chemotherapy than those with PV/SMV invasion or other advanced cancers.

Background/aim: Adrenocortical carcinoma is a very rare tumor characterized by poor prognosis and high mortality. The origin of this tumor is primarily the adrenal cortex. The 5-year overall survival rate of patients with adrenocortical carcinoma has not improved despite therapeutic advances. Early detection of this malignancy remains difficult, and no standard curative therapy currently exists. Therefore, it is important to understand the biology of adrenocortical carcinoma, and to identify prognostic biomarkers and molecular targets for its therapy. DDX39 is an Asp-Glu-Ala-Asp (DEAD)-box RNA helicase, which is required for transcription, splicing and transport of mRNA. There are some reports about overexpression of DDX39 in tumor tissues and cells (lung squamous cell cancer, gastrointestinal stromal tumor, urinary bladder cancer, malignant pleural mesothelioma). However, the clinicopathological involvement of DDX39 in adrenocortical carcinoma has not yet been documented.

Materials and methods: The GEPIA, GEPIA2, and UALCAN platforms were used to analyze DDX39 mRNA expression and survival in patients with adrenocortical carcinoma.

Results: DDX39 was found to be significantly up-regulated in adrenocortical carcinoma tissues, and this up-regulation inversely correlated with prolonged patient survival.

Conclusion: DDX39 may be a potential prognostic biomarker in patients with adrenocortical carcinoma.

Background/aim: The loss of breast cancer cell differentiation during metastatic progression leads to a down-regulation of class 1 human leukocyte antigen (HLA) expression, which in turn hinders cytotoxic T lymphocytes from effectively preventing tumor cell proliferation. Consequently, one would expect that decreased HLA expression would correlate with decreased 5-year survival. However, estrogen receptor alpha (ESR1) is known to be positively associated with overall survival. The study aimed to determine the expression levels of HLA-A, HLA-B/C, and ESR1 and to assess their influence on distant disease-free survival (DDFS).

Materials and methods: This retrospective subgroup analysis of the initial prospective, single-center, double-blind cohort study included a total of 34 patients who underwent a new treatment line for metastatic breast cancer (MBC). The MBC cells were examined using RT-qPCR.

Results: The acquired data and the subsequent survival and ROC analyses indicated a positive association of reduced expression of HLA-A and HLA-B/C with DDFS. A statistically significant association of ESR1 with DDFS could not be shown.

Conclusion: A potential positive association between reduced expression of HLA-A and HLA-B/C and DDFS is observed. This contrasts with the generally observed association between HLA expression loss and poor prognosis, as reported in previous protein-based studies. In metastatic settings, reduced expression of particular HLA subsets, measured at the mRNA level, might have a protective effect against disease progression.