Cancer pathogenesis and therapy最新文献

Background

Lung cancer refers to the occurrence of malignant tumors in the lung, and squamous cell carcinoma is one of the most common pathological types of non-small cell lung cancer. Studies have shown that microRNAs (miRNAs) play an important role in the occurrence, development, early diagnosis, and treatment of lung cancer. This study aimed to explore the role and possible mechanism of MicroRNA-338-3p (miR-338-3p) in lung squamous cell carcinoma (LUSC).

Method

In this study, we compared 238 LUSC patients with relatively high miR-338-3p expression levels with 238 miR-338-3p expression levels in The Cancer Genome Atlas (TCGA)-LUSC dataset using first-line gene set enrichment analysis (GSEA). Second, the mRNA expression of miR-338-3p, FGFR2, and fibroblast growth factor receptor substrate 2 (FRS2) in 30 lung cancers and adjacent lung tissues was detected using quantitative real-time polymerase chain reaction (qRT-PCR). Finally, in vitro experiments were conducted, whereby the expression levels of miR-338-3p in lung cancer cells (H1703, SKMES1, H2170, H520) and normal lung epithelial cells (16HBE) were detected using qRT-PCR. miR-338-3p was overexpressed in lung cancer cells (H1703), and the cell proliferation (cell counting kit-8 [CCK8] assay), colony formation, cell apoptosis, cell cycle (BD-FACSVerse assay, Becton Dickinson, Bedford, MA, USA), cell invasion, and migration (Transwell assay, Thermo Fischer Corporation, Waltham, MA, USA) were detected.

Results

We found that the expression of miR-338-3p was significantly reduced in LUSC tissues (p ​< ​0.001) and cancer cell lines (P < 0.01), and miR-338-3p was significantly negatively correlated with the expression of FGFR2 (P < 0.001) and FRS2 (P < 0.01). Furthermore, overexpression of miR-338-3p inhibited proliferation (P < 0.001), migration, and invasion (P < 0.001) of LUSC cell lines and increased apoptosis in the G1 phase (P < 0.001) and cell cycle arrest (P < 0.05).

Conclusions

Our study demonstrates that miR-338-3p inhibits tumor cell proliferation and migration by targeting FGFR2 and FRS2 in LUSC. We believe that miR-338-3p may be a promising target for the treatment of LUSC.

Therapy development for cancer and cardiovascular disease (CVD) to prolong lifespan makes the relationship between these two conditions more complex. Drug interactions in cardiology and oncology are associated with metabolism and drug transportation. Advances in biomarkers and imaging provide novel methods for detecting cardiotoxicity, including cardiac injury and inflammation. The new concept of CVD-related cancer risk is leading to a new direction of progression termed “reverse cardio-oncology.”

Immune thrombocytopenia (ITP) is common in the elderly. Because of the coexistence of multiple diseases, there are many reservations regarding corticosteroid use in the elderly. Thrombopoietin (TPO) and its analogs can promote platelet production, but it is often difficult to correct TP in a short period. Recombinant human TPO (rh-TPO) acting on the cell membrane and the small-molecule TPO-receptor (MPL) agonist acting on the transmembrane receptor may have synergistic effects and accelerate platelet production because of different sites of action in the signaling pathway. In this study, two elderly patients with refractory ITP were successfully treated with two TPO-MPL signaling pathway agonists: recombinant human thrombopoietin (rh-TPO) and eltrombopag. This combination is safe with rapid and lasting effects. However, in elderly patients with refractory, recurrent, and glucocorticoid contraindications, the combination of different TPO agonists' clinical efficacy and adverse reactions needs to be further evaluated.

Background

Several prognostic biomarkers have been validated for acute myeloid leukemia (AML), a heterogeneous hematopoietic malignancy. However, the factors associated with the cumulative incidence of relapse (CIR) and leukemia-free survival (LFS) in real-world patients with AML have not been well defined.

Methods

This study examined clinical and mutational data of 246 patients with newly diagnosed AML who received the traditional “3 ​+ ​7” regimen in PLA General Hospital from January 2008 to August 2020. Factors associated with CIR and LFS in patients newly diagnosed with AML were analyzed using next-generation sequencing.

Results

Additional sex combs-like 1 (ASXL1) and Serine/arginine-rich splicing factor 2 (SRSF2) mutations were found to be associated with an increased risk of CIR and a reduced LFS in univariate analysis, while only SRSF2 mutations were associated with these factors in the multivariate analysis. Hyperleukocytosis maintained an independent effect on LFS in the multivariate analysis. Hematopoietic stem cell transplantation conferred a significant prognostic benefit on both CIR and LFS in our cohort. Furthermore, we validated the risk classification of patients with AML receiving traditional induction regimens across a broad age range. Based on next-generation sequencing results, we concluded that SRSF2 mutations were predictive of an increased risk of relapse, inferior LFS rates, and non-relapse mortality in patients with newly diagnosed AML.

Conclusion

These findings indicate that patients with SRSF2 mutations might not benefit from the conventional “3 ​+ ​7” regimen. Our results may help in developing molecular stratification strategies and could guide treatment decisions for patients with newly diagnosed AML.

Background

Rituximab combined with cyclophosphamide, doxorubicin hydrochloride, vincristine, and prednisone (R–CHOP) regimen has improved the survival of diffuse large B-cell lymphoma (DLBCL) patients worldwide, compared with CHOP alone. Several limitations were seen in previous studies of Chinese DLBCL patients treated with R–CHOP or R-CHOP-like regimens. This study aimed to investigate the clinical characteristics and treatment outcomes of Chinese DLBCL patients treated with the standard first-line treatment.

Methods

Clinical data were collected from DLBCL patients who received frontline R–CHOP or R-CHOP–like regimens at the Cancer Hospital Chinese Academy of Medical Sciences & Peking Union Medical College (CHCAMS) between January 1, 2005, and December 31, 2018. The treatment outcomes were compared with those of patients diagnosed with DLBCL between 2004 and 2017 and who received immunochemotherapy from the United States Surveillance, Epidemiology, and End Results (SEER) database. Survival rates were estimated using the Kaplan–Meier method and compared using the log-rank test. Multivariate analysis of progression-free survival (PFS) and overall survival (OS) was performed using Cox proportional hazard regression.

Results

Overall, 1084 patients from the CHCAMS and 4013 patients from the SEER database were included in the study. As of April 30, 2022, the median follow-up period for the CHCAMS group was 87.3 (range: 0.5–195.4) months. For the CHCAMS group, the 5-year PFS and OS rates were 61.7% (95% confidence interval [CI]: 58.8–64.7%) and 70.6% (95% CI: 67.8–73.4%), respectively. For the SEER group, the 5-year OS rate was 66.5% (95% CI: 65.0–68.0%), which was inferior to that of the CHCAMS group (P ​< ​0.001). After adjusting for clinical factors and treatment, no significant difference was observed in the OS between the CHCAMS and SEER groups (P ​= ​0.867). In the CHCAMS group, multivariate analysis showed that an Eastern Cooperative Oncology Group performance status score ≥2, presence of B symptoms, Ann Arbor stage III–IV, elevated serum β2-microglobulin levels, and bulky mass were independent adverse prognostic factors affecting PFS and OS (P ​< ​0.05). Additionally, patients aged over 60 years, elevated lactate dehydrogenase levels, and more than two extranodal sites were independent adverse prognostic factors for OS (P ​< ​0.05). Local radiotherapy was significantly associated with better PFS (P ​< ​0.001) and OS (P ​= ​0.001).

Conclusion

After adjusting for clinical and treatment-related factors, no significant difference was observed in the 5-year OS rate between Chinese DLBCL patients treated with standard first-line treatment and those from the SEER database.

Background

Postoperative radiotherapy after conservative surgery for patients with breast cancer usually includes focal over-irradiation (boost) to the surgical bed (SB). Irradiation planning using computed tomography (CT) is difficult in many cases because of insufficient intrinsic soft tissue contrast. To ensure appropriate radiation to the tumor, large boost volumes are delineated, resulting in a higher dose to the normal tissue. Magnetic resonance imaging (MRI) provides superior soft tissue contrast than CT and can better differentiate between normal tissue and the SB. However, for SB delineation CT images alone remain the pathway followed in patients undergoing breast irradiation. This study aimed to evaluate the potential advantages in boost dosimetry by using MRI and CT as pre-treatment imaging.

Methods

Eighteen boost volumes were drawn on CT and MRI and elastically co-registered using commercial image registration software. The radiotherapy treatment plan was optimized using the CT volumes as the baseline. The dose distributions of the target volumes on CT and MRI were compared using dose-volume histogram cutoff points.

Results

The radiation volumes to the SB varied considerably between CT and MRI (conformity index between 0.24 and 0.67). The differences between the MRI and CT boost doses in terms of the volume receiving 98% of the prescribed dose (V98%) varied between 10% and 30%. Smaller differences in the V98% were observed when the boost volumes were delineated using MRI.

Conclusion

Using MRI to delineate the volume of the SB may increase the accuracy of boost dosimetry.

Background

Small cell lung cancer (SCLC) is a highly malignant and aggressive neuroendocrine tumor. With the rise of immunotherapy, it has provided a new direction for SCLC. However, due to the lack of prognostic biomarkers, the median overall survival of SCLC is still to be improved. This study aimed to explore novel biomarkers and tumor-infiltrating immune cell characteristics that may serve as potential diagnostic and prognostic markers in SCLC.

Methods

Gene expression profiles from patients with SCLC were downloaded from the Gene Expression Omnibus (GEO) database, and tumor microenvironment (TME) infiltration profile data were obtained using CIBERSORT. The robust rank aggregation (RRA) method was utilized to integrate three SCLC microarray datasets downloaded from the GEO database and identify robust differentially expressed genes (DEGs) between normal and tumor tissue samples. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed to explore the functions of the robust DEGs. Subsequently, protein–protein interaction networks and key modules were constructed by Cytoscape, and hub genes were selected from the whole network using the plugin cytoHubba. Survival analysis of hub genes was performed by Kaplan–Meier plotter in 18 patients with extensive-stage SCLC.

Results

A total of 312 robust DEGs, including 55 upregulated and 257 downregulated genes, were screened from 129 SCLC tissue samples and 44 normal tissue samples. GO and KEGG enrichment analyses revealed that the robust DEGs were predominantly involved in human T-cell leukemia virus 1 infection, focal adhesion, complement and coagulation cascades, tumor necrosis factor (TNF) signaling pathway, and ECM-receptor interaction, which are closely associated with the development and progression of SCLC. Subsequently, three DEGs modules and six hub genes (ITGA10, DUSP12, PTGS2, FOS, TGFBR2, and ICAM1) were identified through screening with the Cytoscape plugins MCODE and cytoHubba, respectively. Immune cell infiltration analysis by the CIBERSORT algorithm revealed that resting memory CD4⁺ T cells were the predominant infiltrating immune cells in SCLC. In addition, Kaplan–Meier plotter revealed that the gene prostaglandin-endoperoxide synthase 2 (PTGS2) was a potential prognostic biomarker of SCLC.

Conclusions

Hub genes and tumor-infiltrating immune cells may be the molecular mechanisms underlying the development of SCLC, and this finding could contribute to the formulation of individualized immunotherapy strategies for SCLC.

The adaptive arm of the immune system is crucial for appropriate antitumor immune responses. It is generally accepted that clusters of differentiation 4⁺ (CD4⁺) T cells, which mediate T helper (Th) 1 immunity (type 1 immunity), are the primary Th cell subtype associated with tumor elimination. In this review, we discuss evidence showing that antitumor immunity and better prognosis can be associated with distinct Th cell subtypes in experimental mouse models and humans, with a focus on Th2 cells. The aim of this review is to provide an overview and understanding of the mechanisms associated with different tumor outcomes in the face of immune responses by focusing on the (1) site of tumor development, (2) tumor properties (i. e., tumor metabolism and cytokine receptor expression), and (3) type of immune response that the tumor initially escaped. Therefore, we discuss how low-tolerance organs, such as lungs and brains, might benefit from a less tissue-destructive immune response mediated by Th2 cells. In addition, Th2 cells antitumor effects can be independent of CD8+ T cells, which would circumvent some of the immune escape mechanisms that tumor cells possess, like low expression of major histocompatibility-I (MHC-I). Finally, this review aims to stimulate further studies on the role of Th2 cells in antitumor immunity and briefly discusses emerging treatment options.

Background

Autologous hematopoietic stem cell (HSC) transplantation remains the recommended treatment for eligible patients with multiple myeloma (MM). Increasing the number of transplanted CD34⁺ cells shorten the time to hematopoietic reconstitution and increases the overall survival of patients. With the harvest of a sufficient CD34⁺ cell number being crucial, this study aimed to predict the factors that affect stem cell collection.

Methods

We conducted a retrospective study of 110 patients who were newly diagnosed with MM and underwent autologous HSC collection at Beijing Jishuitan Hospital between March 2016 and July 2022. Multiple factors were analyzed using the Mann–Whitney U tests for between-group comparisons. Differences were considered statistically significant at P ​< ​0.05.

Results

We found that patient age affected stem cell collection significantly; for patients younger than 55 years, the number of CD34+ cells harvested may be ​≥ ​2 ​× ​10⁶/L, is unlikely to reach 5 ​× ​10⁶/L. Platelet count at initial mobilization was a predictor of the number of CD34⁺ cells collected. Collection may fail when the platelet count at initial mobilization is below 177 ​× ​10⁹/L and may be excellent when it is higher than 199 ​× ​10⁹/L.

Conclusions

This finding could guide us to predict the approximate number of CD34⁺ cells collected in advance during autologous transplant mobilization for MM and to decide in advance whether to apply plerixafor to improve the number of HSCs collected.