World Journal of Oncology最新文献

Background: Uncoupling protein 2 (UCP2) is essential for maintaining redox homeostasis and regulating energy metabolism. Abnormal expression of UCP2 has been associated with various tumors, including leukemia. Genipin (GEN), a specific inhibitor of UCP2, has a long history of use in traditional Chinese medicine. However, the precise role and underlying mechanisms of UCP2 in the inhibition of leukemia cells by GEN remain inadequately understood. This study focuses on the expression levels of UCP2 in myeloid leukemia (ML) and investigates the effects of GEN on the proliferation, mitochondrial function, and energy metabolism of the chronic myeloid leukemia (CML) cell line K562.

Methods: The expression of UCP2 in clinical samples and cell lines (HL-60, U937, and K562) was confirmed using real-time quantitative polymerase chain reaction (qPCR) and western blot. The effects of GEN on K562 cell viability, morphology, and apoptosis were assessed through a cell counting kit-8 (CCK-8), Wright-Giemsa staining, and an annexin V-fluorescein isothiocyanate/propidium iodide (FITC/PI) apoptosis detection kit. Additionally, the impact of GEN on mitochondrial function and energy metabolism, including reactive oxygen species (ROS), mitochondrial membrane permeability transition pore (MPTP), lactic acid (LA), oxygen consumption rate (OCR), and adenosine triphosphate (ATP) levels in K562 cells, was also examined.

Results: The results showed that UCP2 was differentially expressed in clinical samples from patients with ML. Among the three cell lines examined, K562 cells exhibited a significantly higher expression level of UCP2. Functionally, GEN markedly inhibited K562 cell viability while promoting K562 cell differentiation and apoptosis. Mechanistically, UCP2 mRNA and protein expression levels were inhibited by GEN in K562 cells in a concentration- and time-dependent manner. Additionally, GEN dramatically increased ROS generation and induced mitochondrial MPTP opening in K562 cells. Furthermore, GEN significantly reduced LA production in K562 cells and markedly increased OCR and ATP production.

Conclusion: The results suggest that UCP2 is differentially expressed in ML patients and cell lines; GEN, a UCP2 inhibitor, induces mitochondrial damage and metabolic remodeling, thereby inhibiting proliferation and promoting apoptosis in K562 cells, and thus could be suggested as an adjuvant of an antitumor metabolic therapy.

The investigation of microRNAs (miRNAs) for the purpose of identifying biomarkers and new treatments for breast cancer has been gaining traction from scientists in recent years. Of all the miRNAs, miR-155 has been reportedly involved in breast cancer development as it regulates various cellular processes such as glucose uptake, proliferation, metastasis, and migration. Various efforts have been done towards researching miR-155 as a biomarker in breast cancer; however, the results were varied. The objective of the current systematic review is to compile and summarize information regarding miR-155 as a potential diagnostic biomarker for breast cancer. All eligible studies were found from SCOPUS and PubMed databases. Out of the 376 potential eligible records, only 26 original articles were selected for further assessment according to inclusion and exclusion criteria. The expressions of miR-155 in serum, plasma, biopsy, urine, nipple aspirate fluid, serum exosomes, and peripheral blood mononuclear cells were recorded and analyzed. Besides that, the expression of miR-155 was also correlated to clinicopathological features in breast cancer patients. The area under the curve (AUC) values from receiver operating characteristic (ROC) analysis used to evaluate diagnostic sensitivity and specificity of miR-155 as a diagnostic biomarker were also recorded. The limitations such as the small sampling size, the unemployment of internal controls for quantitative real-time polymerase chain reaction (RT-qPCR), and inconsistency of sensitivity as well as specificity values of miR-155 as a biomarker have been discussed. The present study proposed that miR-155 is a good diagnostic biomarker for breast cancer; however, further clinical research is required to assess the validity of miR-155 as a potential biomarker to translate the research outcomes into clinical practice.

Background: While mutations in the PIK3CA gene play important roles in human breast carcinogenesis, PIK3R1 gene alterations are recognized as actionable mutations for clinical cancer treatment. We aimed to elucidate the role of PIK3R1 in cell proliferation on breast carcinoma and to correlate the PIK3R1 expression with patients' outcome using human tumor tissue arrays.

Methods: Using human BT-474 (estrogen receptor (ER)+/human epidermal growth factor receptor 2 (HER2)-high) breast carcinoma cell line as in vitro model, the role of PIK3R1 in cell proliferation was elucidated by knock-down of the PIK3R1 gene (ΔPIK3R1) in this cell line. Between January 2000 to December 2015, the records of a cohort of 440 patients in our hospital were retrospectively reviewed, including patients' survival. The correlations between PIK3R1 expression and patient prognosis, such as overall survival (OS) and disease-free survival (DFS), were elucidated by human breast cancer tumor tissue array immunostaining.

Results: After the PIK3R1 gene was silenced in the BT-474 line, there was an increased cell number and a decrease in the G0G1-fraction, and increased S-fraction and the S+G2M-fraction for the ΔPIK3R1-BT-474 cell line, as compared to their cell wild type (WT) line. Western blot analysis showed that decreased PIK3R1 protein levels were accompanied by an increase of the p-AKT and p-mTOR proteins in the ΔPIK3R1-BT-474 cell line, compared to the equivalent WT line. Using a human tumor tissue array, patients with high-expressed PIK3R1 protein had better outcomes in terms of DFS and OS, compared to those with low-expressed PIK3R1 protein, when breast cancer was at an early stage (stage I/II), but not across all stages of breast cancer in human patients.

Conclusions: We concluded that downregulated PIK3R1 in BT-474 cells resulted in an increased cell growth and upregulated AKT-mTOR signaling. Clinically, the high-expressed PIK3R1 protein in tumors correlates positively with patients' outcome in stage I and II breast cancer.

Background: The significance of histological grading and peritumoral edema (PTE) in predicting intracranial meningioma recurrence among Saudis is often neglected. This study aimed to evaluate the impact of these factors over a 10-year follow-up period.

Methods: A retrospective cohort of 124 patients with intracranial meningioma was analyzed over the period from 2011 to 2021. All patients underwent gross total resection (GTR) of the tumor. Post-surgical radiotherapy (RT) was offered to patients with grade II-III meningiomas. The impact of histological grading, PTE, and RT on the recurrence-free interval (RFI) was investigated.

Results: The mean age of the patients was 49 years (range: 18 - 84), with 87 females (70.2%) and 37 males (29.8%). Most tumors (88.7%, n = 110) were supratentorial, while 11.3% (n = 14) were infratentorial. The World Health Organization (WHO) grading classified 101 tumors (81.5%) as grade I, 17 (13.7%) as grade II, and six (4.8%) patients as grade III. Grading was significantly associated with RFI (P = 0.013), with grade I meningiomas having the slowest recurrence. The overall recurrence rate was 16.9%, with 38.1% (n = 8) of grade I and 61.9% (n = 13) of grade II-III meningiomas recurring within 5 years post-GTR and RT. There was no significant difference in RFI between RT-exposed and non-exposed patients (P = 0.15). PTE was present in 76 cases (61.3%) and absent in 48 (38.7%), significantly affecting RFI (P = 0.014), with shorter RFI in PTE cases. Overall, 95.2% (n = 118) of patients survived, while 4.8% (n = 6) died; five had grade II-III, and one had grade I meningioma.

Conclusions: Totally, resected intracranial meningiomas with grade II-III features and PTE were associated with earlier tumor recurrence and poorer patient survival. Post-surgical RT had an insignificant effect on the RFI.

Background: Whey protein's biochemical properties make it an ideal nutritional supplement for patients with cancer, especially in perioperative care. Thus, the present study aims to assess the efficacy of whey protein supplementation (WPS) compared to standard care in enhancing postoperative outcomes for patients undergoing comprehensive surgical staging for gynecological cancer.

Methods: In an open-label, randomized controlled trial conducted at Rajavithi Hospital between November 28, 2023 and July 8, 2024, 61 patients scheduled for comprehensive surgical staging were enrolled. Participants were randomized in a 1:1 ratio to either the WPS group (n = 30) or the control group (n = 31). The WPS group received isolated whey protein powder (20 g of protein per serving), administered at 6 pm before surgery and 6 am on the first postoperative day. The control group received standard postoperative care. The primary endpoint was the length of hospital stay (LOHS), with secondary outcomes including gastrointestinal function recovery, postoperative analgesic use, complications, and potential WPS-related adverse events such as transaminitis, acute kidney injury, and electrolyte imbalances.

Results: The WPS group had a significantly shorter LOHS than the control group (79.0 ± 6.7 vs. 93.3 ± 28.4 h, P = 0.021). Additionally, the WPS group demonstrated significant improvements in gastrointestinal function, with shorter times to first flatus (P < 0.001), first defecation (P = 0.013), and first ambulation (P = 0.043). No significant differences were observed between the groups regarding postoperative analgesic use or complications, including fever, nausea/vomiting, wound infection, and readmission (P > 0.05). Furthermore, no WPS-related adverse events were reported.

Conclusion: The use of WPS in the perioperative operative management of gynecological cancer surgery yields promising results by significantly reducing the LOHS and accelerating the recovery of gastrointestinal function while maintaining a favorable safety profile.

Background: Anaplastic thyroid carcinoma (ATC) is the most aggressive thyroid gland malignancy. Several consensuses support the concept of multimodal therapy that combines surgery, radiation, chemotherapy, and targeted therapy. However, patient's comorbidity, poor performance status, and metastasis often make it impossible for patients to undergo multimodal therapy. Therefore, this study aimed to evaluate the survival analysis of ATC patients with different therapeutic modalities.

Methods: This study was a retrospective cohort study using data from the Cancer Registry in our institution. All patients with ATC who visited Prof Ngoerah Hospital between 1998 and 2024 were included in this study. Data regarding the survival duration of patients who received treatment modalities, and clinical data were analyzed using SPSS 20.0 with Kaplan-Meier and log-rank tests.

Results: Forty-two subjects with ATC were included in the analysis, of which 57.1% were female, with a mean age of 62.57 ± 13.42 years old. The median survival is 27.5 days. This study found no association between survival time and clinical characteristics of the patients (P > 0.05). This study found that patients who received combination therapy such as surgery + chemotherapy/radiotherapy (RT) had a longer survival time (64 days), compared to other patients who received surgery only (26 days), chemotherapy/RT only (49 days), or patients who died before receiving any therapy (19 days). However, the log-rank test showed that it was not statistically different (P > 0.05).

Conclusion: ATC survival rates have remained low, and aggressive strategies are still needed to improve the prognosis.

Background: Thymidine kinases (TKs) are key enzymes involved in DNA synthesis and repair, with alterations in their expression associated with various cancers. Thymidine kinase 1 (TK1) and TK2 are cytosolic enzyme proteins that catalyze the addition of a gamma-phosphate group to thymidine. The existing literature on TK1 in cervical squamous cell carcinoma (CESC) fails to address the clinical role of TK1 overexpression and its possible molecular mechanism in CESC. The clinical significance of TK2 in CESC is also unknown. The objective was to explore the differential expression, clinical significance, and molecular mechanisms of TK1 and TK2 in CESC.

Methods: The researchers collected global high-throughput data, extracted the expression levels of TK1 and TK2, and calculated the integrated standardized mean difference (SMD) and summarized receiver's operating characteristics (sROC) of TK1 or TK2 mRNA to investigate the expression profiles of TK genes fully and objectively in 918 CESC tissues and 360 control tissues. In-house tissue microarrays for immunohistochemical testing were used to verify the protein level of TK1 in 62 CESC tissues and control tissues. The growth effect of TK1 and TK2 in CESC cell lines was assessed using Chronos dependency scores derived from CRISPR knockout screen in the Achilles project. We also analyzed the potential mechanism of TK genes by studying the relationship between TK gene expression and immune infiltration, gene alternations as well as the related signal pathways.

Results: The various detection methods employed all confirmed that the TK1 expression is upregulated and TK2 is downregulated in CESC tissues (SMD: 2.44, 95% confidence interval (CI): 1.36 - 3.51, area under curve (AUC): 0.88, 95% CI: 0.85 - 0.90; SMD: -0.69, 95% CI: -1.25 to -0.14, AUC: 0.75, 95% CI: 0.71 - 0.78). Inhibition of TK1 expression by CRISPR knockout had negative influence on the biological functions of 11 CESC cell lines. The expression of TK2 was negatively correlated with the malignant progression of CESC. Expression of TK genes showed significant association with the immune infiltration of macrophages, CD4⁺ T cells, and neutrophils. Genes related with TK1 or TK2 were involved in pathways related to DNA replication, proteasome, and homologous recombination.

Conclusions: Clinically, these findings suggest that the differential expression of TK1 and TK2 could serve as potential biomarkers, as well as therapeutic targets for personalized treatment strategies in CESC patients.

Background: The correlation between methylation of paired box gene 1 (PAX1) and sex determining region Y-box 1 (SOX1) with human papillomavirus (HPV) infection and the progression of cervical lesions is not well understood. This study aims to explore the potential value of PAX1 and SOX1 as diagnostic biomarkers for cervical diseases.

Methods: A total of 139 cervical biopsy tissue samples were obtained from the Department of Pathology, the Seventh Medical Center, Chinese PLA General Hospital from 2021 to 2023. The samples include 32 cases of chronic cervicitis (inflammation group), 30 cases of low-grade squamous intraepithelial lesions (LSIL group), 50 cases of high-grade squamous intraepithelial lesions (HSIL group), and 27 cases of cervical squamous cell carcinoma (CSCC group). DNA was extracted from paraffin-embedded tissues, and the levels of HPV infection and methylation of PAX1 and SOX1 were detected.

Results: The methylation index (M-index) of PAX1 and SOX1 in the HSIL and CSCC groups is significantly higher than in the inflammation group (both P < 0.0001), with no significant difference between the LSIL and inflammation groups. There is no significant difference in the positive PAX1 and SOX1 methylation rate with HPV infection and age. The positive rates of PAX1 methylation in the inflammation, LSIL, HSIL, and CSCC groups were 3.13%, 10.00%, 44.00%, and 88.89%, respectively. The positive rates of SOX1 methylation were 3.13%, 10.00%, 40.00%, and 77.78%, respectively, and increasing with the progression of cervical lesions (R² = 0.9189/R² = 0.9279, P < 0.0001/P < 0.0001). Comparing LSIL, HSIL, and CSCC with the inflammation group and using cervical biopsy pathology diagnosis as the gold standard, methylation of PAX1 and SOX1 is a risk factor for HSIL and CSCC, with odds ratio (OR) values significantly increasing as lesions progress. The sensitivity of PAX1 and SOX1 methylation to cervical lesions increases with the progression of the lesions.

Conclusions: Methylation of SOX1 and PAX1 is not associated with HPV infection. The positive rate of methylation for SOX1 and PAX1 is positively correlated with cervical lesions, which can serve as potential biomarkers for HSIL and CSCC. They are risk factors and potential screening indicators for HSIL and above cervical lesions.

Background: We here investigated the value of imaging examination in evaluating tumor remission-based surgery in patients with head and neck squamous cell carcinoma (HNSCC), who had undergone neoadjuvant immunotherapy combined with chemotherapy (NICC).

Methods: HNSCC patients who underwent NICC and surgery from May 2021 to September 2023 were retrospectively analyzed. All patients had to undergo imaging examination evaluation, including enhanced computed tomography (CT) and enhanced magnetic resonance (MR) imaging before and after NICC. Data related to clinical parameters, complete response of the primary site (PrCR), complete response of the primary site and the lymph node (PLCR), complete response of the lymph node (LCR), and tumor response (TR), were gathered. The paired Chi-square test and t-test were conducted to analyze the differences in responses between imaging examination and pathology. Binary logistic regression was applied to analyze the relevant clinical factors of differences in responses.

Results: In total, data of 41 patients were included in this study. Significant discordant responses were observed between enhanced CT, magnetic resonance imaging (MRI), and pathology in PrCR (4.9%, 7.3% vs. 41.5%), LCR (12.2%, 7.3% vs. 53.7%), PLCR (0%, 0% vs. 31.7%), and TR (severe 29.3%,17.1% vs. 25.61%) (P < 0.05). Patients with hypopharyngeal cancer (odds ratio (OR): 7.04), oral cancer (OR: 3.64), higher neutrophil to lymphocyte ratio (NLR) (OR: 2.05), and earlier T stage (OR: 0.71) exhibited a larger response difference between enhanced CT and pathology. Patients with younger age (OR: 0.79) hypopharyngeal cancer (OR: 22.81), oral cancer (OR: 2.65), higher NLR (OR: 19.47), and earlier T stage (OR: 0.29) exhibited a larger response difference between enhanced MR and pathology.

Conclusions: Discordant responses were noted between the imaging examination and surgical pathology of HNSCC after NICC. Hypopharyngeal cancer, higher NLR, and earlier T stage may predict a higher response difference.

Background: The prognosis for urothelial carcinoma remains poor, with limited therapeutic options, emphasizing the need for further research into targeted therapies. The prognostic and predictive significance of human epidermal growth factor receptor 2 (HER2) expression in urothelial carcinoma remains unclear, with previous studies reporting conflicting results.

Methods: We conducted a retrospective analysis of advanced urothelial carcinoma cases diagnosed between January 2017 and December 2022. HER2 status was prospectively determined using the Leica CB11 antibody on available biopsy specimens. Patient data, tumor characteristics, and survival outcomes were retrieved from hospital records for analysis.

Results: Of the 84 patients initially identified with muscle-invasive disease, HER2 immunohistochemistry (IHC) was performed on 50 samples. Among these, 54% exhibited HER2 scores ≥ 1+, with 22% classified as HER2-positive (3+ score by IHC), 10% as equivocal (2+ score by IHC), and 22% as HER2-low (1+ score by IHC). The distribution of HER2 score ≥ 1+ tumors included 25.7% in the bladder, 20.0% in the renal pelvis, and none in the ureter. HER2-positive (3+ score by IHC) tumors were all histological grade 3. Among these patients, 13.4% presented with localized disease, 20% with locally advanced disease, and 50% with metastatic disease at the time of diagnosis. Notably, 42.8% of recurrent tumors originating from the renal pelvis and 62.5% of those from the bladder exhibited HER2 scores ≥ 1+. Among patients diagnosed with non-metastatic disease, 100% with renal pelvis tumors and 75% with bladder tumors experienced metastatic recurrence if they were HER2-positive (3+ score by IHC). The overall survival for HER2-negative patients was 31.0 months (95% confidence interval (CI): 15.29 - 66.70) compared to 13.0 months (95% CI: 7.32 - 18.68) in the HER2 score ≥ 1+ population (P = 0.0029).

Conclusions: In this cohort of Mexican patients with urothelial carcinoma, HER2 expression was observed in 54.4% of cases. HER2-positive (+3 by IHC) tumors were associated with higher histological grade and worse prognostic outcomes, including increased recurrence, progression, and mortality.