World Journal of Oncology最新文献

Background: Asciminib is approved for treating patients with chronic-phase chronic myeloid leukemia who were previously treated with two or more tyrosine kinase inhibitors or those with T315I mutation. However, the mechanisms underlying asciminib resistance remain unclear.

Methods: In this study, we established a new asciminib-resistant cell line. We examined BCR::ABL1 gene mutation analysis and the effects of conventional chronic myelogenous leukemia inhibitors.

Results: Direct sequencing revealed Y139D and T315I mutations in asciminib-resistant cells. Ponatinib and omacetaxine were effective against asciminib-resistant cells.

Conclusions: Y139D and T315I mutations are extremely resistant to asciminib. Ponatinib and omacetaxine show potential for treating asciminib-resistant chronic myeloid leukemia.

Background: Ovarian function suppression (OFS) treatment causes breast cancer patients' estrogens to fall rapidly to postmenopausal levels, and the 5-year treatment duration and 28-day treatment cycles place a heavy physical and psychological symptom burden on them, which in turn directly or indirectly affects the survival benefit. Managing symptom burden early in treatment is critical, but OFS-related studies have yet to be seen. Self-management is essential for patients' symptom burden. However, self-help management is hampered by patients' lack of knowledge, skills, motivation, etc. Guided self-help intervention (GSH) provides a feasible approach. Empowerment theory is a promising theoretical framework to guide self-management.

Methods: A prospective two-arm parallel randomized controlled single-blind clinical trial will be conducted to investigate the effect of symptom burden GSH based on empowerment theory in breast cancer patients in the early stages of OFS treatment. A block randomization method is used to allocate 144 patients to either the control or intervention group. The program is conducted according to the OFS return-to-hospital treatment cycle. The intervention group will receive a total of two rounds and five sessions of empowering GSH, lasting at least 15 weeks in total; the control group will receive only usual nursing care. Symptom burden and related metrics will be assessed at baseline and 1, 3, and 6 months after OFS treatment, and changes between and within groups will be explored. This paper adhered to the SPIRIT and CONSORT guidelines.

Conclusion: These results will help to validate the GSH in symptom burden management for breast cancer patients in OFS treatment early stages. It enriches its symptom burden management research and may provide implications for the whole cycle of OFS treatment patients.

Background: Peritoneal carcinomatosis (PC) is one of the most unfavorable sites of metastasis for malignant tumors of various localizations, especially gastric cancer (GC). According to the literature, synchronous PC in GC is common in 15-52% of patients. The purpose of this study was to examine the long-term results using personalized systemic and intraperitoneal chemotherapy as part of the combined treatment of stomach cancer presenting with synchronous PC.

Methods: Cytoreductive surgical treatment was performed for 70 patients at the first stage. The control group (n = 35) received standard postoperative chemotherapy according to the FOLFOX scheme. Personalized postoperative systemic and intraperitoneal chemotherapy was administered in the basic group (n = 35), based on the expression levels of the eight genes in the primary tumor, lymph node, and peritoneal metastases.

Results: The median progression-free survival was 14.9 months in the basic group, and in the control group it was 11.2 months (P < 0.001). The median life expectancy in the basic group was 16.8 (13.7 - 18.8) months, in the control group it was 12.5 (11.3 - 13.1) months (P < 0.001).

Conclusions: Developing algorithms of personalized systemic and intraperitoneal chemotherapy in patients with GC with synchronous carcinomatosis, based on the analysis of molecular genetic characteristics of the tumor and metastases, allows to improve the long-term results of combined treatment.

Background: Epithelial ovarian cancer (EOC) is the leading cause of death in gynecological cancers in developed countries. In recent years, there has been a growing need for economical and accurate pretreatment laboratory investigations to assess the prognosis of patients with advanced EOC (AEOC). We aimed to investigate the role of the hemoglobin-albumin-lymphocyte-platelet (HALP) index in suboptimal cytoreduction and oncological outcomes.

Methods: A prognostic prediction model for diagnosing suboptimal cytoreduction for patients with AEOC receiving neoadjuvant chemotherapy (NACT) was developed. Multivariate logistic regression analysis was performed to identify the independent predictors of suboptimal cytoreduction, with a P-value < 0.05, and then transformed into risk-scoring systems. Internal validation was performed using the bootstrapping procedure, and predictive cytoreduction (PSC) scores were compared using non-parametric receiver operating characteristic (ROC) regression. Survival analysis was performed using Kaplan-Meier estimation and Cox proportional regression.

Results: In total, 473 patients were analyzed, and the rate of suboptimal surgery was 43%. A scoring system in predicting suboptimal cytoreduction included age, cancer antigen (CA)-125 level before surgery, performance status, cycles of chemotherapy, peritoneal cancer index, and HALP index ≤ 22.6. The model had good discriminative ability (area under the ROC (AUROC), 0.80; 95% confidence interval (CI), 0.76 - 0.84), outperforming the PSC score (AUROC, 0.75; 95% CI, 0.71 - 0.80). The score was divided into the low-risk (positive predictive value (PPV), 22.4; 95% CI, 17.8 - 27.7), moderate-risk (PPV, 65.9; 95% CI, 56.9 - 74.0), and high-risk (PPV, 90.6; 95% CI, 79.3 - 96.9) groups. The HALP index score of ≤ 22.6 was independently associated with progression-free survival (hazard ratio (HR), 2.92; 95% CI, 1.58 - 5.40) and overall survival (HR, 2.66; 95% CI, 1.57 - 4.49).

Conclusion: The HALP index is a newly predicted factor for suboptimal cytoreduction and oncological outcomes in patients with AEOC after NACT.

Pigs are playing an increasingly vital role as translational biomedical models for studying human pathophysiology. The annotation of the pig genome was a huge step forward in translatability of pigs as a biomedical model for various human diseases. Similarities between humans and pigs in terms of anatomy, physiology, genetics, and immunology have allowed pigs to become a comprehensive preclinical model for human diseases. With a diverse range, from craniofacial and ophthalmology to reproduction, wound healing, musculoskeletal, and cancer, pigs have provided a seminal understanding of human pathophysiology. This review focuses on the current research using pigs as preclinical models for cancer research and highlights the strengths and opportunities for studying various human cancers.

Background: Spinster homologue 2 (SPNS2) is a transporter of sphingosine-1-phosphate (S1P), a bioactive lipid linked to cancer progression. We studied the link between SPNS2 gene expression, tumor aggressiveness, and outcomes in patients with hepatocellular carcinoma (HCC).

Methods: Gene expression in patients with HCC was analyzed from the Cancer Genome Atlas (TCGA) (n = 350) and GSE76427 (n = 115) as a validation cohort, as well as liver tissue cohort GSE6764 (n = 75).

Results: High-SPNS2 HCC was significantly associated with high level of lymph-angiogenesis-related factors. SPNS2 expression was significantly higher in normal liver and early HCC versus advanced HCC (P < 0.02). High SPNS2 levels enriched immune response-related gene sets; inflammatory, interferon (IFN)-α, IFN-γ responses, and tumor necrosis factor (TNF)-α, interleukin (IL)-6/Janus kinase/signal transducer and activator of transcription (JAK/STAT3) signaling, complement and allograft rejection, but did not significantly infiltrate specific immune cells nor cytolytic activity score. High-SPNS2 HCC enriched tumor aggravating pathway gene sets such as KRAS (Kirsten rat sarcoma virus) signaling, but inversely correlated with Nottingham histological grade, MKI67 (marker of proliferation Ki-67) expression, and cell proliferation-related gene sets. Further, high-SPNS2 HCC had significantly high infiltration of stromal cells, showing that low-SPNS2 HCC is highly proliferative. Finally, high-SPNS2 HCC was associated with better disease-free, disease-specific, and overall survival (P = 0.031, 0.046, and 0.040, respectively).

Conclusions: Although SPNS2 expression correlated with lymph-angiogenesis and other cancer-promoting pathways, it also enriched immune response. SPNS2 levels were higher in normal liver compared to HCC, and inversely correlated with cancer cell proliferation and better survival. SPNS2 expression may be beneficial in HCC patients despite detrimental in-vitro effects.

Background: Of various human epidermal growth factor receptor (HER) inhibitors, only the anti-HER2 monoclonal antibody (mAb) Herceptin/trastuzumab and the antibody-drug conjugate trastuzumab deruxtecan (T-Dxd) has been approved for the treatment of patients with stomach cancer. However, the duration of response may be short in many patients, with tumor heterogeneity being one contributing factor.

Methods: We investigated the effect of various types of targeted agents on growth in vitro and migration of a panel of human stomach cancer cells (HSCCLs) and the impact of cell proliferation rate on the anti-tumor activities of these agents. We also investigated the association between the cell surface expression of the HER family members, hepatocyte growth factor receptor (c-Met), anaplastic lymphoma kinase (ALK)7 and cancer stem cell markers CD44 and CD133, and the response to the targeted agents.

Results: Of the 18 agents examined, the cyclin dependent kinase (CDK) 1/2/5/9 inhibitor dinaciclib was the most effective and inhibited the growth of all human HSCCLs at 50% inhibitory concentration (IC₅₀) values between 9 nM to 23 nM. Of various HER inhibitors, the irreversible pan-HER family inhibitors (e.g., afatinib) were more effective than the reversible dual epidermal growth factor receptor (EGFR)/HER2 tyrosine kinase inhibitor (TKI) lapatinib and the EGFR-specific TKI erlotinib in inhibiting the growth of HSCCLs. Of agents targeting different downstream cell signaling molecules, dasatinib targeting Ab1/Src/C-Kit, trametinib targeting MERK1/2 and miransertib targeting AKT1/2/3 inhibited growth of majority of HSCCLs, with the IC₅₀ values ranging from 2 nM to 7 µM. Many of these agents were more effective in inhibiting the growth of HSCCLs when they were proliferating at a slower rate. Treatment with neratinib, afatinib, dinaciclib, dasatinib, stattic, miransertib and paclitaxel significantly inhibited migration of stomach cancer cells. Interestingly, treatment with a combination of afatinib and dasatinib or afatinib and miransertib resulted in synergistic and additive growth inhibition of stomach cancer cells.

Conclusions: These results suggest that treatment with a combination of these agents may be of therapeutic value in stomach cancer and warrants further investigations.

Background: Clostridioides difficile (C. difficile or C. diff) is a toxin-producing bacteria that is notorious for causing life-threatening diarrhea. Recent literature has investigated various effects of Clostridioides difficile infection (CDI) in cancer patients, but research into the impact of CDI on the development of cancer and its effects on the microbiome is limited. CDI predominately affects the colon, which urges consideration into the sequalae of infection. This study investigated the correlation between CDI and the incidence of colorectal carcinoma (CRC).

Methods: A retrospective study (2010 - 2020) was conducted using a Health Insurance Portability and Accountability Act (HIPAA) compliant national database. The International Classification of Disease ninth and 10th Codes (ICD-9, ICD-10), Current Procedural Terminology (CPT), and National Drug Codes were used to identify CRC diagnosis, CDI, and matching or control parameters. Patients were matched for age, sex, Charlson Comorbidity Index (CCI), region of residence, and CDI treatment. An additional, but separate, query was executed to include obese patients with and without CDI, who were similarly matched and assessed for CRC. Statistical analyses were implemented to assess significance and estimate odds ratios (ORs).

Results: CDI was associated with a decreased incidence of CRC (OR = 0.59, 95% confidence interval (CI): 0.55 - 0.63), and the difference was statistically significant (P < 2.2 × 10^-16). CDI treatment, including appropriate antibiotics and fecal microbiota transplant (FMT), was controlled for in both infected and noninfected populations. Patients with a prior CDI who received relevant treatment were compared to patients with no history of CDI and received analogous treatment. Both populations subsequently developed CRC. Results remained statistically significant (P < 2.2 × 10^-16) with a relative risk (RR) of 0.57 (95% CI: 0.54 - 0.60). Obesity was explored as a controlled variable in relation to CRC development in patients with and without prior CDI. Obese patients without a history of CDI were found to have a decreased risk of developing CRC. Results were statistically significant (P < 4.3 × 10^-13) with an OR of 0.70 (95% CI: 0.63 - 0.77).

Conclusions: This study shows a statistically significant correlation between CDI and decreased incidence of CRC. Additionally, there is a statistically significant correlation between obese patients with CDI and an increased incidence of CRC. Further research is needed to explore the mechanism of this striking relationship and the implications of CDIs on the microbiome.

Background: Cervical cancer remains the most lethal and prevalent cancer among women. Obstructive uropathy is a common complication of advanced cervical cancer, caused by the expanding tumor. One of the recommended treatments for this condition is the implantation of a double J (DJ) stent. However, this procedure is challenging due to the unique characteristics of the patient. The objective of this study was to identify the variables that influence the successful insertion of a DJ stent in women with advanced cervical cancer.

Methods: This retrospective study included women who attempted to have a DJ stent implanted at the General Hospital of Adam Malik in Medan, Indonesia, between January 2020 and December 2022, and were diagnosed with advanced cervical cancer. The inclusion criteria were limited to cervical cancer patients in stages III-IV, according to the International Federation of Gynecology and Obstetrics (FIGO) staging standard, who underwent an attempt at DJ stent insertion. Patients who underwent a nephrostomy and received a DJ stent were excluded from the study. The participants were divided into two groups based on the success of the DJ stent implantation. The analysis was conducted using the logistic regression test and the Chi-square test.

Results: The study included 88 patients with advanced-stage cervical cancer, of whom 45 underwent nephrostomy and 43 received a DJ stent. The analysis revealed that lower levels of hydronephrosis (odds ratio (OR): 18.203, P = 0.001), urea (OR: 4.207, P = 0.037), and creatinine (OR: 6.923, P = 0.004), higher levels of urine output (OR: 8.26, P = 0.003), and lower cervical cancer stage (OR: 4.125, P = 0.022) were all predictors of successful DJ stent insertion.

Conclusion: For women with advanced cervical cancer, lower degrees of hydronephrosis, urea, and creatinine levels, higher urine output, and lower cervical cancer stage were all predictive factors for successful DJ stent implantation.

Background: DNA damage-induced apoptosis suppressor (DDIAS) has recently been discovered to induce cancer progression, but its functions and mechanisms in glioma have not been well studied.

Methods: DDIAS expression in glioma tissues was analyzed by the Gene Expression Profiling Interactive Analysis server (GEPIA) and the Gene Expression database of Normal and Tumor tissue 2 (GENT2) databases. The role of DDIAS in glioma progression was studied by short hairpin RNA (shRNA) targeting DDIAS. The effects of DDIAS on glioma cell viability, cell proliferation, invasion, migration, and tumor sphere formation were determined by cell counting kit-8 (CCK-8), EdU, Transwell, tumor spheroid formation, extreme limiting dilution analysis assays in vitro and xenograft model construction in vivo. In addition, RNA sequencing and further functional experiments were used to analyze the DDIAS regulatory mechanism in glioma.

Results: We found that DDIAS was highly expressed in glioma and that upregulated DDIAS indicated poor prognosis. Functionally, DDIAS knockdown inhibited glioma cell viability, cell proliferation, invasion and migration in vitro and tumor growth in vivo. In addition, lymphoid enhancer-binding factor 1 (LEF1) was identified as the downstream effector of DDIAS by RNA sequencing. DDIAS downregulation inhibited LEF1 mRNA and protein expression. The expression of DDIAS and LEF1 was positively correlated, and LEF1 overexpression rescued the inhibitory phenotype induced by DDIAS downregulation. We further showed that DDIAS downregulation inhibited cyclin A1, vimentin and the stemness-related factor CD133 and decreased the sphere formation capability, but these features were rescued by upregulation of LEF1.

Conclusion: Taken together, these findings suggest that DDIAS promotes glioma progression and stemness by inducing LEF1 expression, proving that DDIAS may be a potential target for the treatment of glioma.