Clinical and Translational Oncology最新文献

Background

Biliary tract cancers are serious diseases and new biomarkers may be useful for the optimal management and prediction of these cases. This study aimed to evaluate the prognostic significance of the hemoglobin, albumin, lymphocyte, and platelet (HALP) score, a novel composite marker, in patients with metastatic biliary tract cancer.

Methods

Patients with biliary tract cancers were analyzed retrospectively. Laboratory values, patient and disease characteristics, and survival rates were evaluated. The diagnostic impact of the HALP score was assessed with regression analyses.

Results

The study included 106 individuals with metastatic biliary tract cancer. Based on the median HALP score, ≥ 2.22 was considered a high score and < 2.22 was considered low. The overall average survival time was found to be 11.4 months. Patients with low HALP scores had median overall survival of 9.5 months, while those with high HALP scores had median overall survival of 15.9 months. In multivariate analysis, Eastern Cooperative Oncology Group performance status, CA19-9 level, and HALP score remained significant predictors of overall survival.

Conclusion

The HALP score appears to be a useful prognostic marker in patients with metastatic biliary tract cancer.

Focal adhesion kinase (FAK) expression has been linked to tumor growth, immunosuppression, metastasis, angiogenesis, and therapeutic resistance through kinase-dependent and kinase scaffolding functions in the nucleus and cytoplasm. Hence, targeting FAK alone or with other agents has gained attention as a potential therapeutic strategy. Moreover, mounting evidence shows that FAK activity can influence the tumor immune microenvironment crosstalk to support tumor progression. Recently, tumor immune microenvironment interaction orchestrators have shown to be promising therapeutic agents for cancer immunotherapies. Therefore, this review highlights how FAK regulates the tumor immune microenvironment interplay to promote tumor immune evasive mechanisms and their potential for combination therapies with standard cancer treatments.

Background

Monocarboxylate transporter 4 (MCT4) is a novel biomarker related to the level of immune cell infiltration, but its impact on tumor immune microenvironment (TIME) of colorectal liver oligometastases (CLO) remains unclear. The aim of this study was to assess MCT4 expression in primary tumor and liver oligometastases, investigate its impact on immune cell infiltration and its prognostic value for CLO patients undergoing liver resection.

Methods

We retrospectively selected 135 CLO patients who underwent curative liver resection between June 1999 and December 2016, and samples included 74 primary tumor tissues and 122 liver metastases. Immunohistochemistry (IHC) was performed to detect MCT4 expression in paraffin-embedded specimens and tyramine signal amplification (TSA) was used to detect the density of tumor-infiltrating lymphocytes, including CD3 + , CD8 + and Foxp3 + . Recurrence-free survival (RFS) and overall survival (OS) were analyzed using the Kaplan–Meier method and log-rank test, and independent prognostic factors were identified with Cox regression modeling.

Results

Survival analysis indicated that CLO patients with low MCT4 expression had better 3-year RFS and 3-year OS rates than those with high MCT4 expression. Multivariate analysis indicated that high MCT4 expression was independently associated with poor RFS and OS. High MCT4 expression was associated with a lower number of intratumoral CD3 + /CD8 + T cells and was associated with higher Foxp3 + T cells infiltration. Patients with low MCT4 expression and high levels of differential immune infiltration had longer survival.

Conclusions

MCT4 overexpression was associated with an unfavorable prognosis in patients with CLO and MCT4 expression level had an impact on intratumoral immune infiltration degree. A novel parameter that combined MCT4 expression level and differential immune infiltration level was constructed to stratify patients with CLO into different risk groups.

Theragnostic is a type of precision medicine that uses molecules linked to radioactive isotopes for the diagnosis and treatment of diseases. In recent years, it has gained significant importance to treat neuroendocrine tumors and is currently being used in prostate cancer. Various radiopharmaceuticals have emerged for diagnosing and detecting lesions showing prostate-specific membrane antigen (PSMA) positivity on the Positron emission tomography/computed tomography scan, being the most widely used labeled with [⁶⁸Ga] and [¹⁸F]. Its use as therapy in prostate cancer (PC) has been assessed in the VISION, TheraP, and PSMAfore clinical trials conducted with the radioligand [¹⁷⁷Lu]Lu-PSMA-617, demonstrating significant antitumor activity. The aim of this article is to present practical recommendations, based on current available scientific evidence and on a multidisciplinary consensus, for the diagnosis and treatment with [¹⁷⁷Lu]Lu-PSMA-617 in patients with PC.

Background

Globally, breast cancer is the most common type of malignant tumor. It has been demonstrated that TMEM41A is abnormally expressed in a number of cancers and is linked to a dismal prognosis. TMEM41A's involvement in breast cancer remains unknown, though.

Methods

Data from databases such as TCGA were used in this study. Expression differences were compared using non-parametric tests. Cox regression analysis was employed, and analyses such as Nomogram were used to assess the significance of TMEM41A in predicting the prognosis of breast cancer. Lastly, it was looked into how immune cell infiltration in breast cancer is related to TMEM41A expression levels.

Results

The results suggest that TMEM41A is overexpressed in breast cancer and correlates with poor prognosis (P = 0.01), particularly in early-stage and ductal A breast cancer (P < 0.01). Breast cancer patients' expression of TMEM41A was found to be an independent risk factor (HR = 1.132, 95% CI 1.036–1.237) by multifactorial Cox regression analysis. The Nomogram prediction model's c-index was 0.736 (95% CI 0.684–0.787). The results of GSEA biofunctional enrichment analysis included the B cell receptor signaling pathway (P < 0.05). Ultimately, there was a significant correlation (P < 0.05) between TMEM41A expression in breast cancer and an infiltration of twenty immune cells.

Conclusions

Breast cancer tissues overexpress TMEM41A, which is linked to immune cell infiltration and prognosis (particularly in early stage and luminal A breast cancer). Overexpression of TMEM41A is anticipated to serve as a novel prognostic indicator and therapeutic target for breast cancer.

Background

It is well established that smoking is the most significant risk factor for bladder cancer, yet the impact of smoking on the recurrence and progression of non-muscle-invasive bladder cancer (NMIBC) remains a contentious issue.

Objective

To review all relevant literature published to date, providing a comprehensive assessment of the effects of smoking on the recurrence and progression of NMIBC, thereby offering a basis for smoking cessation management in NMIBC patients.

Methods

A search was conducted for all relevant literature published up to April 2024 in PubMed, Web of Science, and Embase databases. The existing literature results and deficiencies were analyzed, and the gaps in understanding between different studies were highlighted, with recommendations for future research.

Results

A total of 24 studies were included in this work. Among them, 14 studies suggested that smoking promotes the recurrence and progression of NMIBC, while another 10 studies concluded that smoking has no effect on the recurrence and progression of NMIBC patients.

Conclusions

Our research indicates that smoking increases the risk of recurrence and progression in NMIBC patients, and quitting smoking can improve health-related quality of life. High-quality, large-sample prospective cohort studies (or randomized controlled studies) are still needed in the future.

Purpose

This study aims to identify patient subgroups who benefit more from perioperative immunotherapy combined with chemotherapy (IO-CT) based on clinical and molecular characteristics in resectable non-small cell lung cancer (NSCLC).

Methods

Randomized controlled trials (RCTs) on perioperative IO-CT were searched. Beneficial differences of IO-CT regimens across different patient subgroups were assessed by pooling trial-specific ratios in event-free survival (EFS), overall survival (OS), pathological complete response (pCR), and major pathological response (MPR).

Results

Six studies (n = 3003) involving five IO-CT regimens were included. Compared to CT alone, all IO-CT regimens significantly improved EFS, OS, MPR, and pCR, but increased toxicity. Toripa-chemo showed the best EFS and nivo-chemo showed the best OS. Patients with PD-L1 ≥ 1% had more EFS benefits compared to those with PD-L1 < 1% (HR [hazard ratio]: 1.55, 95% CI 1.17–2.04). Squamous NSCLC patients had significantly more pCR and MPR benefits than non-squamous NSCLC patients (pCR: OR [odds ratio] 0.68, 95% CI 0.49–0.95; MPR: OR 0.61, 95% CI 0.45–0.82). Former smokers had significantly higher pCR benefits than non-smokers (OR: 2.18; 95% CI 1.21–3.92). Additionally, OS benefit was significantly higher in patients < 65 years compared to those ≥ 65 years (HR ratio: 0.59, 95% CI 0.36–0.95). For MPR, males benefited significantly more from IO-CT compared to females (OR: 1.69, 95% CI 1.18–2.42).

Conclusion

Perioperative IO-CT is more effective but more toxic than CT alone in resectable NSCLC. Patients with PD-L1 ≥ 1%, squamous NSCLC, a history of smoking, age < 65 years and male gender may experience greater benefits from perioperative IO-CT.

The anti-cancer mechanism of High-dose Vitamin C (HDVC) is mainly to participate in the Fenton reaction, hydroxylation reaction, and epigenetic modification, which leads to the energy crisis, metabolic collapse, and severe peroxidation stress that results in the proliferation inhibition or death of cancer cells. However, the mainstream view is that HDVC does not significantly improve cancer treatment outcomes. In clinical work and scientific research, we found that some drugs or therapies can significantly improve the anti-cancer effects of HDVC, such as PD-1 inhibitors that can increase the anti-cancer effects of cancerous HDVC by nearly three times. Here, the adjuvant and intensive therapy and synergistic mechanisms including HDVC combined application of chemoradiotherapies multi-vitamins, targeted drugs, immunotherapies, and oncolytic virus are discussed in detail. Adjuvant and intensive therapy of HDVC can significantly improve the therapeutic effect of HDVC in the metabolic treatment of cancer, but more clinical evidence is needed to support its clinical application.

Background

The impact of age on the causes of death (CODs) in patients with early-stage intrahepatic cholangiocarcinoma (ICC) who had undergone surgery was analyzed in this study.

Methods

A total of 1555 patients (885 in the older group and 670 in the younger group) were included in this study. Before and after applying inverse probability of treatment weighting (IPTW), the different CODs in the 2 groups were further investigated. Additionally, 7 different machine learning models were used as predictive tools to identify key variables, aiming to evaluate the therapeutic outcome in early ICC patients undergoing surgery.

Results

Before (5.92 vs. 4.08 years, P < 0.001) and after (6.00 vs. 4.08 years, P < 0.001) IPTW, the younger group consistently showed longer overall survival (OS) compared with the older group. Before IPTW, there were no significant differences in cholangiocarcinoma-related deaths (CRDs, P = 0.7) and secondary malignant neoplasms (SMNs, P = 0.78) between the 2 groups. However, the younger group had a lower cumulative incidence of cardiovascular disease (CVD, P = 0.006) and other causes (P < 0.001) compared with the older group. After IPTW, there were no differences between the 2 groups in CRDs (P = 0.2), SMNs (P = 0.7), and CVD (P = 0.1). However, the younger group had a lower cumulative incidence of other CODs compared with the older group (P < 0.001). The random forest (RF) model showed the highest C-index of 0.703. Time-dependent variable importance bar plots showed that age was the most important factor affecting the 2-, 4-, and 6-year survival, followed by stage and size.

Conclusions

Our study confirmed that younger patients have longer OS compared with older patients. Further analysis of the CODs indicated that older patients are more likely to die from CVDs. The RF model demonstrated the best predictive performance and identified age as the most important factor affecting OS in early ICC patients undergoing surgery.

Background

Aberrant expression of apelin receptor (APLNR) has been found to be involved in various cancers’ development, however, its function in prostate cancer (PCa) remains unclear. The research aimed to investigate the role and potential mechanism of APLNR in PCa.

Methods

The mRNA expression of APLNR was detected via qRT-PCR assay. PCa cell proliferation and apoptosis were determined through plate cloning and flow cytometry. In addition, the expression of apoptosis-related proteins (Bax, Bcl-2, and cleaved caspase-3) was evaluated using western blot. DNA damage marker (γ-H2AX) was analyzed by immunofluorescence and western blot. GSEA analysis was performed for seeking enrichment pathways of APLNR in PCa, and the protein levels of PI3K, p-PI3K, AKT, p-AKT, mTOR, and p-mTOR were tested using western blot.

Results

APLNR expression was up-regulated in PCa tissues and cells. Silencing APLNR enhanced the sensitivity of PCa cells to radiotherapy, which was manifested by inhibiting cell proliferation, promoting cell apoptosis, and promoting DNA damage. Next, silencing APLNR inhibited the PI3K/AKT/mTOR pathway. Specifically, 740Y-P (the PI3K/AKT/mTOR pathway activator) reversed the effects of silencing APLNR on PCa cell proliferation, apoptosis and DNA damage.

Conclusion

Silencing APLNR inhibited cell proliferation, promoted cell apoptosis, and enhanced the radiosensitivity of PCa cells, which was involved in the PI3K/AKT/mTOR signaling pathway. This study is conducive to the deeper understanding of PCa and further provides a new perspective for the treatment of PCa.