Incidence, clinical features, and survival outcomes of primary malignant lacrimal gland tumors: A population-based analysis.

BACKGROUND: Studies on the epidemiological information and prognosis of primary malignant lacrimal gland tumors (MLGTs) are rare for its low occurrence. The goal of our research was to investigate the epidemiological characteristics and survival outcomes of patients with MLGTs. METHODS: Incidence and demographic information of patients with MLGTs were collected from the Surveillance, Epidemiology, and End Results (SEER) database. To identify independent prognostic factors for disease-specific survival (DSS) and overall survival (OS), univariate and multivariate Cox regression analysis were performed. RESULTS: The overall incidence of primary MLGTs from 1975 to 2020 was 0.413/1,000,000 (according to the 2000 American standard population), with a steadily increasing incidence over years. A total of 964 patients with primary MLGTs were diagnosed, with an average age of 59.3 years. Of these, 53.2% were aged ≥60 years, 57.4% were female, and 77.1% were whites. Multivariate Cox regression analysis demonstrated that year of diagnosis, age, sex, histological type, SEER stage, surgery, and chemotherapy were independent prognostic factors of DSS or OS. CONCLUSIONS: Although primary MLGT is rare, its incidence has steadily increased in the past 46 years, and surgery was related to a better prognosis.

Research progress on the immune microenvironment and immunotherapy in gastric cancer.

The tumor microenvironment, particularly the immune microenvironment, plays an indispensable role in the malignant progression and metastasis of gastric cancer (GC). As our understanding of the GC microenvironment continues to evolve, we are gaining deeper insights into the biological mechanisms at the single-cell level. This, in turn, has offered fresh perspectives on GC therapy. Encouragingly, there are various monotherapy and combination therapies in use, such as immune checkpoint inhibitors, adoptive cell transfer therapy, chimeric antigen receptor T cell therapy, antibody-drug conjugates, and cancer vaccines. In this paper, we review the current research progress regarding the GC microenvironment and summarize promising immunotherapy research and targeted therapies.

Single-cell sequencing in primary intraocular tumors: understanding heterogeneity, the microenvironment, and drug resistance.

Retinoblastoma (RB) and uveal melanoma (UM) are the most common primary intraocular tumors in children and adults, respectively. Despite continued increases in the likelihood of salvaging the eyeball due to advancements in local tumor control, prognosis remains poor once metastasis has occurred. Traditional sequencing technology obtains averaged information from pooled clusters of diverse cells. In contrast, single-cell sequencing (SCS) allows for investigations of tumor biology at the resolution of the individual cell, providing insights into tumor heterogeneity, microenvironmental properties, and cellular genomic mutations. SCS is a powerful tool that can help identify new biomarkers for diagnosis and targeted therapy, which may in turn greatly improve tumor management. In this review, we focus on the application of SCS for evaluating heterogeneity, microenvironmental characteristics, and drug resistance in patients with RB and UM.

Epidemiology and survival outcomes of patients with orbital region non-cutaneous squamous cell carcinoma: a population-based analysis.

Background: Non-cutaneous squamous cell carcinoma (ncSCC) of the orbital region is very rare. Thus, its epidemiological characteristics and prognosis are poorly understood. The aim of the study was to assess the epidemiological characteristics and survival outcomes of ncSCC of the orbital region. Methods: Incidence and demographic data on ncSCC of the orbital region were extracted from the Surveillance, Epidemiology, and End Results (SEER) database and analyzed. The chi-square test was used to calculate the differences between groups. Univariate and multivariate Cox regression analyses were performed to determine the independent prognostic factors for disease-specific survival (DSS) and overall survival (OS). Results: The overall incidence of ncSCC in the orbital region from 1975 to 2019 was 0.68/1,000,000, and the incidence showed an increasing trend during this period. A total of 1,265 patients with ncSCC of the orbital region (mean age, 65.3 years) were identified in the SEER database. Of these, 65.1% were aged ≥60 years, 87.4% were White, and 73.5% were male. The conjunctiva (74.5%) was the most common primary site, followed by the orbit (12.1%), lacrimal apparatus (10.8%), and overlapping lesion of the eye and adnexa (2.7%). Multivariate Cox regression analysis revealed that age, primary site, SEER summary stage, and surgery were independent prognostic factors for DSS, whereas age, sex, marital status, primary site, SEER summary stage, and surgery were independent prognostic factors for OS. Conclusions: The incidence of ncSCC in the orbital region has increased over the past 40 years. It usually affects White people, men, and people aged ≥60 years, and its most common site is the conjunctiva. Orbital SCC has worse survival outcomes than SCC of other sites in the orbital region. Surgery is the independent protective treatment for ncSCC of the orbital region.

The next bastion to be conquered in immunotherapy: microsatellite stable colorectal cancer.

Colorectal cancer (CRC) is the second leading cause of cancer-related deaths worldwide, and its incidence continues to rise, particularly in developing countries. The advent of immune checkpoint inhibitors (ICIs) has represented a significant advancement in CRC treatment. Deficient mismatch repair (dMMR) or high microsatellite instability (MSI-H) serves as a biomarker for immunotherapy, with dMMR/MSI-H CRC exhibiting significantly better response rates to immunotherapy compared to proficient mismatch repair (pMMR)or microsatellite stable (MSS) CRC. While some progress has been made in the treatment of pMMR/MSS CRC in recent years, it remains a challenging issue in clinical practice. The tumor microenvironment (TME) plays a crucial role not only in the development and progression of CRC but also in determining the response to immunotherapy. Understanding the characteristics of the TME in pMMR/MSS CRC could offer new insights to enhance the efficacy of immunotherapy. In this review, we provide an overview of the current research progress on the TME characteristics and advancements in immunotherapy for pMMR/MSS CRC.

Effect of miR-184 and miR-205 on the tumorigenesis of conjunctival mucosa associated lymphoid tissue lymphoma through regulating RasL10B and TNFAIP8.

AIM: To explore the effect of miR-184 and miR-205 on the proliferation and metastasis of conjunctival mucosa associated lymphoid tissue (MALT) lymphoma. METHODS: Tissue of tumor and adjacent normal control from 5 patients with conjunctival MALT was included. RPMI8226 cell line was selected to verify the effect of miRNAs in B cells. The function of microRNA on the RPMI8226 cell apoptosis, migration and invasion was evaluated by apoptosis assay and Transwell assay. The mRNA and protein expression were examined by quantitative RT-PCR and Western blotting. The effect of microRNA on regulation of downstream gene expression was evaluated by luciferase report assay. RESULTS: A decreased level of miR-184 and miR-205 was observed in MALT lymphoma tissue. Exogenous miR-184 and miR-205 analogues promoted apoptosis, and inhibited the survival, migration, and invasion of RPMI8226 cells. miR-184 and miR-205 inhibitor reversed the process. The RNA and protein level of RasL10B and TNFAIP8 were downregulated in MALT lymphoma tissue. The exogenous of miR-184 and miR-205 promoted the expression of RasL10B and TNFAIP8. Meanwhile, inhibition of miR-184 and miR-205 repressed the expression of target gene, RasL10B and TNFAIP8. CONCLUSION: miR-184 and miR-205 suppresses the tumorigenesis of conjunctival MALT lymphoma through regulating RasL10B and TNFAIP8.

CD34- Orbital Fibroblasts From Patients With Thyroid-Associated Ophthalmopathy Modulate TNF-α Expression in CD34+ Fibroblasts and Fibrocytes.

Purpose: Orbital fibroblasts from patients with Graves' disease (GD-OF) express many different cytokines when treated with bovine thyrotropin (bTSH). The present study aimed to determine why TNF-α cannot be induced by bTSH in GD-OF. Methods: Fibrocytes and GD-OFs were cultivated from donors who were patients in a busy academic medical center practice. Real-time PCR, Western blot analysis, reporter gene assays, cell transfections, mRNA stability assays, ELISA, and flow cytometry were performed. Results: We found that bTSH induces TNF-α dramatically in fibrocytes but is undetectable in GD-OF. The induction in fibrocytes is a consequence of increased TNF-α gene promoter activity and is independent of ongoing protein synthesis. It could be attenuated by dexamethasone and the IGF-1 receptor inhibiting antibody, teprotumumab. When separated into pure CD34+ OF and CD34- OF subsets, TNF-α mRNA became highly inducible by bTSH in CD34+ OF but remained undetectable in CD34- OF. Conditioned medium from CD34- OF inhibited induction of TNF-α in fibrocytes. Conclusions: Our data indicate that CD34- OF appear to release a soluble(s) factor that downregulates expression and induction by bTSH of TNF-α in fibrocytes and their derivative CD34+ OF. We proffer that CD34- OF produce an unidentified modulatory factor that attenuates TNF-α expression in GD-OF and may do so in the TAO orbit.

Common Immunosuppressive Monotherapy for Graves' Ophthalmopathy: A Meta-Analysis.

BACKGROUND: Several immunosuppressive therapeutic regimens are widely used to treat Graves' ophthalmopathy (GO), including oral glucocorticoids (OGC), intravenous glucocorticoids (IVGC), retrobulbar injections of glucocorticoids (ROGC) and orbital radiotherapy (OR). The priority among these is unknown. This meta-analysis investigated the efficacy and tolerability of the above regimens. METHODS: The PubMed, EMBASE, and Cochrane Library databases and the Chinese Biomedicine Database were searched up to November 18, 2014. Randomized controlled trials (RCTs) comparing monotherapies (OGC, IVGC, ROGC and OR) in patients with moderate-to-severe active GO were selected. The main efficacy measures were the response rate, the standard mean difference (SMD) in the reduction in the clinical activity score (CAS) and the mean difference (MD) in proptosis from baseline to the end of treatment. The main tolerability measure was the risk ratio (RR) for adverse events. The pooled estimates and 95% confidence intervals (95% CIs) were calculated using the RevMan software, version 5.1. RESULTS: Seven published RCTs involving 328 participants were included in the present meta-analysis, including IVGC versus OGC (3 trials), ROGC versus OGC (3 trials) and OR versus OGC (1 trial). IVGC was more effective than OGC in response rate (RR = 1.48, 95% CI = 1.18-1.87) and had an obvious CAS reduction (SMD = 0.69, 95% CI = 0.13-1.25). IVGC caused fewer adverse events than OGC. ROGC and OGC had no statistically significant difference in response rate (RR = 1.16, 95% CI = 0.94-1.42). OR also did not differ significantly compared with OGC (RR = 0.93, 95% CI = 0.54-1.60). ROGC and OR had fewer adverse events, such as weight gain, compared with OGC. CONCLUSIONS: For patients with GO in the moderate-to-severe active phase, current evidence gave priority to IVGC, which had a statistically significant advantage over OGC and caused fewer adverse events. ROGC and OR did not provide greater efficacy than OGC, although better tolerability and fewer adverse events were shown.