Anticancer research最新文献

Background/aim: The dysregulation of matrix metalloproteinase (MMP) proteins has been reported to be involved in the etiology of pterygium. However, studies about the role of matrix metalloproteinase-11 (MMP-11) are lacking. This study is the first to examine the genomic role of MMP-11 in pterygium.

Materials and methods: The genotypes of MMP-11 rs738791, rs2267029, rs738792, and rs28382575 were determined in 140 pterygium cases and 280 non-pterygium controls by utilizing polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and direct sequencing.

Results: The genotypic frequencies of MMP-11 rs738792 TT, CT and CC were 40.0%, 50.7%, and 9.3% in the pterygium group, significantly different from those in the non-pterygium group (55.0%, 37.1%, and 7.9%, respectively; p for trend=0.0139). Specifically, individuals carrying the variants CT and CC had a 1.88- and 1.63-fold odds ratio of pterygium risk [95% confidence interval (CI)=1.22-2.89 and 0.77-3.44, p=0.0054 and 0.2834, respectively]. In the dominant model, individuals carrying CT+CC had significantly higher pterygium risk (odds ratio=1.83, 95%CI=1.21-2.77, p=0.0052). No association was found for other MMP-11 polymorphisms. Allelic analysis showed that MMP-11 rs738792 C allele was significantly associated with pterygium risk (odds ratio=1.48, 95%CI=1.08-2.01, p=0.0169). for the variant alleles of other MMP-11 polymorphisms were not associated with pterygium risk.

Conclusion: The MMP-11 rs738792 genotypes can serve as a predictive marker for pterygium risk in Taiwanese. Additionally, elucidating the role of MMP-11 in the pathogenesis of pterygium could inform targeted therapies based on MMP-11 modulation.

Background/aim: Testicular cancers, particularly seminomas and non-seminomas, generally have a favorable prognosis, although a small subset of patients experience mortality. Current knowledge of clinical markers associated with relapse and poor prognosis in seminoma is limited. Chemokines, key proteins in the tumor microenvironment, are underexplored in seminoma prognosis. Additionally, tumor-infiltrating lymphocytes (TILs), which play a critical role in cancer prognosis, require further investigation in the context of seminoma.

Patients and methods: Samples from 25 seminoma patients and 24 control patients who underwent orchiectomy were immunohistochemically (IHC) stained for chemokines CXCR4, CXCR5, and their ligands CXCL12, CXCL13, and the proliferation marker Ki-67. The associations between IHC results and clinical presentations were examined.

Results: Chemokine profiles differed between seminoma and normal testis. The expression of chemokines in TILs in seminoma samples was especially over-expressed. The cytoplasmic expression of CXCL13 in TILs multiplied by the percentage of TILs in each sample, appeared to approach statistical significance concerning the likelihood of relapse.

Conclusion: The involvement of TILs in seminoma biology warrants further investigation, especially their role in the tumor micro-environment and pathogenesis. Chemokine and Ki-67 expression in TILs could serve as potential markers for assessing seminoma prognosis.

Background/aim: The membrane-bound protein lymphocyte antigen 6 family member D (LY6D), a marker of early B cell lineage is reportedly expressed in several human malignancies and has been implicated in cancer stemness. However, its expression and role in cancer stemness remain largely unexplored in pancreatic ductal adenocarcinoma (PDAC). The aim of this study was to clarify the role of LY6D in PDAC.

Materials and methods: We conducted functional analysis of LY6D to evaluate its impact on the malignant features of PDAC cells in vitro. Using our in-house developed stem cell separation technique, which isolates cells with low proteasome activity and CD44 v9 cell surface marker for cancer stem cells, we performed sphere formation and chemosensitivity tests and tumor formation assay in mice, through knockdown of LY6D expression. Immuno-histopathological analysis was also conducted to reveal the clinical significance of LY6D in PDAC.

Results: In vitro functional assays demonstrated that LY6D was critically involved in promoting the cancer malignant phenotype, including increased invasive ability, drug resistance, migration capacity, and cancer stemness. Immunohistopathological analysis revealed that high LY6D expression levels were associated with high recurrence rates and poorer prognosis in PDAC.

Conclusion: Our study showed that LY6D is a novel prognostic indicator and plays a key role in regulation of cancer stemness in PDAC.

Background/aim: Family with sequence similarity 83 member G (FAM83G) plays an important role in cancer aggressiveness and patients' prognosis across various types of cancer. However, the association of FAM83G protein expression in breast cancer with clinicopathologic factors, breast cancer subtypes, and prognosis is not well characterized. This study aimed to elucidate the clinical significance of FAM83G protein expression in breast cancer.

Materials and methods: Immunohistochemistry was employed to examine FAM83G protein expression in 75 breast cancer tissues, assessing its potential as a biomarker for breast cancer patients. The Kaplan-Meier plotter was used to estimate the correlation between FAM83G mRNA expression and survival outcomes in TNBC patients.

Results: FAM83G protein was predominantly localized in the cytoplasm of breast cancer cells, exhibiting uniform expression throughout tumor tissues. FAM83G expression was significantly higher in cancerous areas compared to non-cancerous areas. High FAM83G expression was more prevalent in triple-negative breast cancer (TNBC) cases than in hormone receptor-positive cases. Although high FAM83G protein expression did not significantly impact prognosis in our cohort, a large-scale database analysis revealed an association between high FAM83G expression and poor prognosis in TNBC cases.

Conclusion: This study demonstrates an association between high FAM83G expression in breast cancer tissues and TNBC. FAM83G may serve as a promising biomarker and therapeutic target for breast cancer patients.

Background/aim: Vascular invasion (VI) in colorectal carcinoma (CRC) is an independent prognostic feature and a high-risk indicator for adjuvant chemotherapy in stage II CRC. This study evaluated the effect of elastic staining on VI detection.

Patients and methods: The VI was assessed using elastic staining in 154 patients with CRC. Based on hematoxylin and eosin (H&E) staining, cases were classified into three groups: absent (n=80), equivocal (n=23), and suspected (n=51). Two sections per case were evaluated for VI using elastic staining, and the presence of VI on one or both slides was confirmed. Finally, the correlation between the VI and other clinicopathological factors was analyzed.

Results: The overall detection rate of VI using elastic staining was 67/154 (51.4%). VI was detected in 17/80 (21.3%), 3/23 (13.0 %), and 47/51 (92.2%) patients in the absent, equivocal, and suspected groups, respectively. VI was detected in both sections of the elastic staining slides in 28 cases, and in only one section in 38 cases. The VI was significantly associated with perineural invasion, M stage, and synchronous metastasis.

Conclusion: VI detection using H&E staining alone is not reliable, emphasizing the importance of elastic staining in improving VI detection. Therefore, we recommend the incorporation of elastic staining into routine pathological practice for all pT3 and pT4 CRC cases.

Glioblastoma (GBM) is categorized by the World Health Organization (WHO) as a grade 4 glioma and is a uniformly fatal tumor of the central nervous system. With the discovery of specific gene anomalies, GBM classification has been modified several times to provide better diagnostic and prognostic accuracy. Survival outcomes remain dismal despite the current therapeutic modalities, which include a combination of surgical resection, adjuvant chemotherapy, and radiotherapies, providing brief control of tumor progression. GBM remains aggressive and reoccurs primarily due to the presence of a unique population of untreatable glioblastoma stem cells (GSC). The presence of high mutation rates and a dysregulated transcriptional landscape increase GSC resistance to conventional chemotherapy and radiation therapy, contributing to poor outcomes seen in GBM patients. Accordingly, GSCs have emerged as targets of interest in new GBM treatment paradigms. Consequently, it is important to understand their distinct properties, such as GSC interactions with the hypoxic microenvironment, enhancing their growth. The epigenomic regulators and fundamental molecular components of the signaling pathways represent potential targets for GBM therapies. In this review, we aimed to describe the evolution of GBM classification and highlight the current therapeutic modalities, including gene and immunotherapies, and mammalian target of rapamycin (mTOR) inhibitors to target GBM. Furthermore, we explored the molecular pathway of GSCs and the ongoing investigation of circulating tumor cells (CTC), along with precision therapeutics, which aim to provide novel discoveries and effective treatments for GBM with improved survival.

Background/aim: The pomegranate fruit has been associated with a variety of human health benefits based on its antioxidant and anti-inflammatory properties. Punicic acid (PA) is an omega-5 long chain polyunsaturated fatty acid that constitutes approximately 65-80% of the oil from pomegranate seeds and has been found to possesses anti-cancer activity in various cancer types. To better understand its cell specificity, we investigated the effects of punicic acid on both the MCF-7 human breast cancer cell line as well as the non-cancerous MCF-10A breast epithelial line.

Materials and methods: We treated both cell types with different concentrations of punicic acid and measured viable cell density, cytotoxicity and apoptosis, as well as peroxiredoxin (Prdx) antioxidant expression.

Results: We found that punicic acid was cytotoxic to both lines, but MCF-10A cells demonstrated higher levels of cytotoxicity and sensitivity to lower concentrations. We further demonstrated that cytotoxicity was associated with apoptosis in both lines. Using real time PCR, we demonstrated induction of all six Prdx mRNAs in MCF-7 cells, ranging from a 1.4-fold increase with 2 μg/ml, to over a 5-fold increase with 10 μg/ml. In stark contrast, MCF-10A cells exhibited considerably higher induction of all six Prdx mRNAs at 10μg/ml, exceeding a 30-fold induction of Prdx1, Prdx2 and Prdx5.

Conclusion: Our data are the first to demonstrate differential cytotoxicity and Prdx regulation by punicic acid in these two cell lines. These results may provide important insight into cell-specific mechanisms of punicic acid in breast cancer.

Background/aim: Ovarian cancer remains a significant challenge due to its high mortality rate and poor prognosis, especially in advanced stages. Despite treatment advancements, issues with resistance and recurrence persist, highlighting the urgent need for new and effective therapies. This study aimed to evaluate fostamatinib, an oral spleen tyrosine kinase inhibitor initially developed for autoimmune diseases, as a potential treatment for ovarian cancer.

Materials and methods: The effects of fostamatinib on ovarian cancer cell lines were assessed using WST-1 assays for cell proliferation. Apoptosis was evaluated through TUNEL assays, DNA fragmentation analysis, and flow cytometry. Western blot analysis was used to detect cleavage of apoptotic proteins, including caspase-3 and PARP, and flow cytometry analyzed cell cycle changes.

Results: Fostamatinib treatment resulted in a dose- and time-dependent reduction in ovarian cancer cell growth and induced apoptosis, as indicated by increased TUNEL-positive cells, DNA fragmentation, and rises in both early and late apoptosis. Western blot analysis showed increased cleavage of apoptotic proteins, including caspase-3 and PARP. Flow cytometry also demonstrated an increase in the sub-G1 phase of the cell cycle, further supporting apoptosis induction.

Conclusion: Fostamatinib, by inhibiting cell proliferation and inducing apoptosis, shows promise as a repurposed therapeutic agent for ovarian cancer, potentially offering a new approach to improve patient outcomes.

Background/aim: Pseudoaneurysm formation is a potentially fatal complication after pancreaticoduodenectomy. We developed a packing method in which the gastroduodenal artery stump is packed inside a falciform ligament to reduce the post-pancreatectomy hemorrhage due to pseudoaneurysm formation. This study aimed to evaluate its efficacy.

Patients and methods: This study included 210 patients who underwent pancreaticoduodenectomies between January 2007 and December 2023. The study population was divided into two groups; the packing group (n=110) and the no-packing group (n=100), and the clinical variables were compared between the two groups.

Results: Pseudoaneurysms were observed in six (2.9%) patients, and post-pancreatectomy hemorrhage was observed in four (1.9%) patients. There was no significant difference in pseudoaneurysm formation between the packing and no-packing groups (p=0.477), and the mortality rates for both pseudoaneurysm and post-pancreatectomy hemorrhage were zero. Two patients in the no-packing group were found to have shock, whereas four patients in the packing group (n=4) did not. Additionally, we encountered a 6 cm unruptured pseudoaneurysm following packing.

Conclusion: The packing method did not reduce pseudoaneurysm formation after pancreaticoduodenectomy, but may prevent pseudoaneurysm rupture.

Background/aim: Nab-paclitaxel is used to treat patients with pancreatic cancer. However, it frequently induces peripheral neuropathy. Notably, pharmacokinetic factors may be associated with neuropathic symptoms as the onset depends on the cumulative dose. Therefore, we prospectively examined the association between the cumulative dose of nab-paclitaxel at the onset of peripheral neuropathy and polymorphisms of hepatic transporter genes.

Patients and methods: Patients with pancreatic cancer receiving nab-paclitaxel (125 mg/m²) and gemcitabine (1,000 mg/m²) were enrolled. Peripheral neuropathy was assessed using the Common Terminology Criteria for Adverse Events (CTCAE), Patient-Reported Outcomes CTCAE (PRO-CTCAE), and Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT/GOG-Ntx), every 2-12 weeks, and every 4 weeks thereafter. solute carrier organic anion transporter family member 1B1 (SLCO1B1) 521T>C, 388A>G; SLCO1B3 rs11045585; ATP-binding cassette transporters, subfamily B, member 1 (ABCB1) 1236C>T, 2677G>T/A, 3435C>T; ABCC1 rs2644983; ABCC2 24C>T; and ABCG2 421C>A were analyzed by direct sequencing. Correlations between transporter genotypes and cumulative dose at symptom onset were assessed using Kaplan-Meier and log-rank tests.

Results: In total, 25 patients were enrolled. The lowest median cumulative dose for nab-paclitaxel at peripheral neuropathy onset using PRO-CTCAE was 593 mg. By CTCAE it was 800 mg, and by FACT/GOG-Ntx it was 1,090 mg (p<0.0001). At symptom onset, patients with ABCC2 -24C/T genotype had received a significantly lower median cumulative dose by PRO-CTCAE (540 mg) than those with C/C (720 mg) (p=0.0188). However, the other polymorphisms studied were not associated with symptoms.

Conclusion: Herein, we found for the first time that ABCC2 -24C/T genotype was significantly associated with the onset of nab-paclitaxel-induced peripheral neuropathy detected with PRO-CTCAE.