Cancer Medicine最新文献

Objective

Wood dust is a human carcinogen. However, studies examining the relationship between wood dust exposure and laryngeal cancer have yielded inconsistent findings. Therefore, we systematically reviewed relevant studies examining the relationship between wood dust exposure and laryngeal cancer development, followed by a meta-analysis.

Methods

Publications in the following databases were searched: PubMed, Medline, Embase, Cochrane Library, and China National Knowledge Infrastructure (CNKI). The Newcastle–Ottawa scale was used to evaluate the study quality. A random-effects model was used for the meta-analysis.

Results

Eighteen case–control studies and one cohort study, involving a total of 4426 patients with laryngeal cancer and 319,129 control participants, were identified. The association between occupational/environmental exposure to wood dust and laryngeal cancer, if any, was unclear (adjusted combined OR: 1.11; 95% CI: 0.94–1.31). However, subgroup analyses according to the number of cases, geographic region, publication year, and follow-up duration revealed correlations between wood dust exposure correlated and laryngeal cancer, as follows: number of cases > 200 (OR: 1.14; 95% CI: 1.01–1.25 [n = 10]); studies conducted in the US (OR: 1.21; 95% CI: 1.07–1.37 [n = 5]); follow-up time > 5 years (OR: 1.19; 95% CI: 1.07–1.32 [n = 10]); and publication after the year 2000 (OR: 1.15; 95% CI: 1.04–1.28 [n = 8]). A high heterogeneity in the results was observed (I² = 42.5%, p = 0.024). The results were stable, and no publication bias existed, according to sensitivity analysis.

Conclusions

This meta-analysis suggests that wood dust exposure is associated with laryngeal cancer. Additional large-scale studies are warranted to clarify the relationship between wood dust exposure and laryngeal cancer.

Background

Research on circulating tumor cells (CTCs) offers the opportunity to better understand the initial steps of blood-borne metastasis as main cause of cancer-related deaths. Here, we have used the colon cancer CTC-MCC-41 and breast cancer CTC-ITB-01 lines, which were both established from human CTCs as permanent cell lines as models to further study CTC biology with special emphasis on anchorage-independent survival and growth.

Methods and Results

Both cell lines showed a marked intrinsic plasticity to switch between suspension and adherent in vitro growth, in 2D adherent culture conditions, and established an equilibrium of both growth patterns with predominant adherent cells in the CTC-MCC-41 line (77%) and suspension cells in the CTC-ITB-01 line (85%). Western blot analysis revealed a higher expression of pERK1/2 in CTC-ITB-01 adherent cells compared to the suspension counterpart that suggested the involvement of kinases in this process. Subsequent functional kinome profiling identified several serine/threonine as well as tyrosine kinases that were differentially regulated in adherent and suspension CTCs. In the adherent cells of the breast cancer line CTC-ITB-01 the activity of MSK1, Src family kinases and the PKG family was increased compared to the suspension counterpart. In adherent cells of the colorectal CTC-MCC-41 line, an increased activity of TYRO3 and JAK2 was detected, whereas p38 MAPK was strongly impaired in the suspension CTC-MCC-41 cells. Some of the regulated kinases, which include the Src family, TYRO3, MSK1, JAK2 and p38 MAPK, have been associated with crucial cellular processes including proliferation, migration and dormancy in the past.

Conclusions

The investigated CTC lines exhibit a high plasticity, similar to the concept of ‘adherent-to-suspension transition (AST)’ that was recently suggested as a new hallmark of tumor biology by Huh et al. Moreover, we identified differentially regulated kinome profiles that may represent potential targets for future studies on therapeutic interventions.

Background

In the era of novel agents, the clinical outcomes of induction treatment and the impact of the number of high-risk cytogenetic abnormalities (HRA) in newly diagnosed multiple myeloma (NDMM) need to be explored.

Objective

Through this study, we aim to analyze the effectiveness of different induction treatments and explore the survival outcomes of patients with varying numbers of HRA.

Methods

A total of 734 patients from seven medical centers were included in our study.

Results

Patients in the CD38 monoclonal antibody or IMiDs plus proteasome inhibitors (PI) groups had significantly superior overall survival (OS) and progression-free survival (PFS) compared to those receiving IMiDs or PI alone. Additionally, the CD38 monoclonal antibody conferred a PFS advantage over IMiDs plus PI. Patients with ≥ 2 high-risk cytogenetic abnormalities (HRA) exhibited an extremely poor prognosis and should be considered ultra-high-risk individuals in multiple myeloma (MM). The CD38 monoclonal antibody, transplantation, and achieving minimal residual disease (MRD) negativity only partly mitigated the poor prognosis in patients with HRA. Furthermore, patients with 1q21 gain/amplification (1q21+) only had a significantly worse prognosis compared to patients without HRA, and those with 1q21+ plus del17p or t(4;14) exhibited an inferior prognosis compared to those with 1q21+ alone.

Conclusion

Our results suggested that double-hit multiple myeloma was associated with extremely poor survival outcomes, and more effective treatments needed to be explored for this particular subtype of MM.

Background

As one of the most common malignancies, cervical cancer (CC) seriously affects women's health. This study aimed to investigate the biological function of Serinc2 in CC.

Methods

Serinc2 expression was surveyed utilizing immunohistochemistry, western blot, and qRT-PCR. CC cell viability, invasion, proliferation, migration, and apoptosis, were detected via CCK-8, Transwell assay, colony formation, wound healing assay, and flow cytometry. Glucose consumption, lactate production, and ATP levels were determined by the corresponding kit. The protein expression of c-Myc, PDK1, HK2, PFKP, LDHA, Snail, Vimentin, N-cadherin, and E-cadherin was detected via western blot. The interaction between the promoter of PFKP and Myc was confirmed through luciferase reporter assay and Chip assay. In vivo, to evaluate the function of Serinc2 on tumor growth, a xenograft mouse model was used.

Results

In CC tissues and cells, Serinc2 was upregulated. In CC cells, knockdown of Serinc2 suppressed cell invasion, proliferation, migration, decreased the expression of Snail, Vimentin, N-cadherin, HK2, PFKP, LDHA, and PDK1, increased E-cadherin expression, reduced glucose consumption and the production of lactate and ATP, and induced cell apoptosis; Serinc2 overexpression led to the opposite results. Mechanically, Serinc2 promoted Myc expression, and Myc induced PFKP expression. Furthermore, overexpressed Myc abolished the inhibitive influences of Serinc2 knockdown on the malignant behaviors of CC cells. Additionally, knockdown of Serinc2 inhibited tumor growth and reduced the protein expression of c-Myc, PFKP, LDHA, and PDK1 in vivo.

Conclusions

Knockdown of Serinc2 inhibited the malignant progression of CC, which was achieved via Myc pathway. Our study provides novel insight into CC pathogenesis.

Background

The clinical impact of obesity on postoperative outcomes of patients undergoing thyroidectomy remains controversial.

Methods

Patients aged ≥ 18 years who were diagnosed with thyroid malignancy and underwent thyroidectomy between 2016 and 2020 were included, and divided into two groups: patients with body mass index (BMI) < 30 kg/m² and those with BMI ≥ 30 kg/m². Patients in the obese group were then subdivided into four groups: Group 1 (BMI 30.0–34.9 kg/m²), Group 2 (BMI 35.0–39.9 kg/m²), Group 3 (BMI 40.0–44.9 kg/m²), and Group 4 (BMI ≥ 45.0 kg/m²) to evaluate the association between degree of obesity and clinical outcomes. We performed propensity score matching, compared outcome variables between the groups, and conducted adjusted multivariate logistic regression analyses of postoperative outcomes.

Results

A total of 6778 patients diagnosed with thyroid cancer who underwent thyroidectomy were screened, of whom 1299 (19.2%) patients were obese. Patients in the obese group had higher total hospital charges (p < 0.001) and an increased risk of overall postoperative complications (34.7% vs. 30.5%, p = 0.023). Specifically, patients in the obese group had increased odds of respiratory complication (adjusted odds ratio (aOR) 1.66, 95% confidence interval (CI) [1.26–2.19]), acute renal failure (aOR 1.87, 95% CI [1.13–3.09]), and wound complication (aOR 2.77, 95% CI [1.21–6.37]) than those in the non-obese group. Moreover, trend tests showed that the risks of unfavorable discharge, infection, acute renal failure, and respiratory complication all exhibited an upward trend with increased BMI.

Conclusion

Obesity is associated with an increased risk of postoperative complications in patients with thyroid cancer undergoing thyroidectomy. This finding suggests that obese patients should be treated with more caution during postoperative recovery.

Background

The highly homologous T-box transcription factors TBX2 and TBX3 are critical for embryonic development, and their overexpression in postnatal tissues contributes to a wide range of malignancies, including melanoma and rhabdomyosarcoma. Importantly, when TBX2 and TBX3 are depleted in cancers where they are overexpressed, the malignant phenotype is inhibited, and they have therefore been regarded as druggable targets. However, the time and costs associated with de novo drug development are challenging and result in drugs that are costly, especially for patients in low- and middle-income countries. In the current study, we therefore combined a targeted and drug repurposing approach to identify drugs that are expected to be more efficacious and cost-effective with significantly reduced side effects.

Methods

A high-throughput cell-based immunofluorescence screen was performed to identify drugs in the Pharmakon 1600 drug library that can negatively regulate TBX2 and/or TBX3 levels. “Hit” drugs were validated for their effect on TBX2/TBX3 levels and cytotoxicity in TBX2/TBX3-dependent melanoma and rhabdomyosarcoma cells. To this end, immunofluorescence, western blotting, quantitative real-time PCR, and MTT cell viability assays were performed.

Results

Niclosamide, piroctone olamine, and pyrvinium pamoate, were identified as TBX2 and/or TBX3-targeting drugs, and they exhibited cytotoxicity in a TBX2/TBX3-dependent manner. Furthermore, these “Hit” drugs were shown to induce senescence and/or apoptosis.

Conclusions

Niclosamide, piroctone olamine, and pyrvinium pamoate are promising, cost-effective therapeutic agents for the treatment of TBX2/TBX3-dependent cancers.

Objective

This study explored the distributions of gastric mucosal status and their links to gastric cancer within urban high-risk individuals in China.

Methods

From 2014 to 2015, a questionnaire survey was administered among individuals aged 40 to 69 years, residing for over 3 years in seven selected cities across China. Utilizing the questionnaire data, high-risk individuals for gastric cancer were screened. These identified high-risk individuals were invited to undergo endoscopy, followed by pathological examinations conducted for those with suspicious lesions. Prior cancer patients and those newly diagnosed with gastric cancer were excluded, and the remaining endoscopic participants were prospectively followed up until December 2021.

Results

The prospective study followed 8911 individuals at high risk of gastric cancer for a median duration of 6.77 years. The incidence density of gastric cancer was 58.55 per 100,000 person-years. At baseline, the distributions of subjects across normal gastric mucosa, gastritis/ulcer/polyp, atrophic gastritis/intestinal metaplasia, and intraepithelial neoplasia groups were 47.09%, 36.27%, 9.57%, and 7.07%, respectively. Compared with normal gastric mucosa, the hazard ratios (HRs) for gastric cancer in the other groups were 0.89 [95% confidence interval (95%CI): 0.38–2.08], 1.52 (95%CI: 0.50–4.66), and 4.63 (95%CI: 1.98–10.82). When using the 40–54 age group as the reference, the HR for 55–69 age group was 3.49 (95%CI: 1.52–7.98).

Conclusion

Among high-risk individuals with gastric cancer, the proportions of individuals exhibiting different gastric mucosal status inversely correlated with the severity of mucosal lesions, whereas the risk of gastric cancer progressively escalated with the increasing severity of mucosal lesions and advancing age.

Objective

The objective of this study is to investigate the efficacy of behavioral activation (BA), a novel psychological intervention, in ameliorating psychological distress and anxiety symptoms among patients diagnosed with esophageal and gastric cancer, as well as the mediating role of self-efficacy between BA and psychological distress.

Methods

A total of 139 patients diagnosed with esophageal and gastric cancer were recruited in China from March 2023 to October 2023 and randomly assigned to either the BA plus care as usual group (BA+CAU group) or the care as usual group (CAU group). Pre- and post-intervention questionnaires, including the Psychological Distress Thermometer (DT), Generalized anxiety disorder 7-item (GAD-7) Scale, General Self-Efficacy Scale (GSES) and the activation subscale of Behavioral Activation for Depression Scale (BADS-A), were administered.

Results

Generalized estimating equation analyses revealed that, compared to usual care alone, combining BA with usual care significantly ameliorated psychological distress, anxiety as well as improved self-efficacy and activation. The mediation analysis revealed that self-efficacy served as a mediator in the relationship between activation and psychological distress.

Conclusions

BA primarily based on telephone or WeChat can not only directly ameliorates psychological distress and anxiety symptoms in patients with esophageal cancer and gastric cancer but also indirectly alleviates psychological distress by enhancing self-efficacy. The study also demonstrates the potential of BA in cancer patients, a skill that can be effectively acquired by primary care workers without specialized training and implemented more flexible.

Trial Registration: NCT06348940

Background

FOXC1 and ERK1-2 are proteins implicated in aggressive biological behavior of various malignancies including lymphomas.

Material and Methods

We investigate the additive prognostic value of stromal FOXC1 expression and tumor phosphorylated ERK1-2 (pERK1-2) expression to the established National Comprehensive Cancer Network International Prognostic Index (NCCN-IPI), in 92 diffuse large B-cell lymphoma (DLBCL) cases. Multidimensional analysis using statistics and machine learning (ML) models assessed prognostic value of established clinicopathologic variables with stromal FOXC1 and tumor pERK1-2 expressions.

Results

Both high FOXC1 stroma group and high pERK1-2 tumor group were significantly associated with shorter progression-free survival (PFS) and overall survival (OS) compared with low group (p = 0.015, 0.034 and p = 0.025, 0.025 each respectively). In multivariable analysis, high FOXC1 stromal expression was an independent prognostic factor of OS (p = 0.037). The addition of stromal FOXC1 and tumor pERK1-2 to the NCCN-IPI score significantly improved prediction of time to death compared with NCCN-IPI score alone (Harrell's C-index = 0.801 vs. 0.764; p = 0.030). ML models reconfirmed the addition of stromal FOXC1 expression and tumor pERK1-2 to NCCN-IPI score had the highest C-index (0.952) among combinations. Stromal FOXC1 and tumor pERK1-2 were determinants of DLBCL prognosis, whose addition significantly improved prognostic performance of the NCCN-IPI.

Background

Small-cell lung cancer (SCLC) shows high enhancer of zeste homolog 2 (EZH2) expressions. EZH2-mediated epigenetics promote epithelial-mesenchymal transition (EMT), enhancing invasive and metastatic potential in malignancies. MicroRNAs (miRNAs), small noncoding RNAs, modulate EMT, determining tumor phenotypes. However, the association between miRNAs and EZH2 in SCLC remains to be clarified—we aimed to identify a novel tumorigenic mechanism through miRNAs, EZH2, and EMT in SCLC, leading to future therapeutic applications.

Methods

We analyzed EZH2 and E-cadherin expressions in lung cancer cell lines and tumor tissues from 34 SCLC patients and confirmed EZH2 siRNA-mediated EMT inhibition. miRNA expression profiles were compared between EZH2 knockdown SCLC cells and negative control SCLC cells using miRNA array. We identified a target miRNA of EZH2 showing expressional differences in EZH2-knockdown cells and analyzed the impact of the miRNA on EZH2-mediated EMT and tumorigenesis.

Results

All SCLC cells showed increased EZH2 and decreased E-cadherin expressions. SCLC tissues had higher EZH2 and lower E-cadherin expressions than other lung cancer tissues. miRNA array revealed that miR-4448 expression increased in EZH2-knockdown SCLC cells. miR-4448 overexpression reduced tumor cell growth and prevented EMT. miR-4448 bound to the 3′UTR of the girdin gene and suppressed its expression, thereby decreasing Akt phosphorylation at Ser473. Attenuated Akt phosphorylation resulted in AMP-activated protein kinase (AMPK) phosphorylation at Thr172 and 183, enhancing EZH2 phosphorylation at Thr311.

Conclusion

SCLC characterized high EZH2 expression and promoted EMT, compared with non-small cell lung cancer. miR-4448 inhibited Girdin expression, reducing Akt phosphorylation, and enhancing AMPK and EZH2 phosphorylation. Eventually, miR-4448 prevented EZH2-mediated EMT and tumorigenesis by modulating the Girdin/Akt/AMPK axis in SCLC. miR-4448 might be a potential SCLC inhibitor.