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Dermatomyositis represents an autoimmune disorder characterized by notable skin and muscular manifestations. The annual incidence of dermatomyositis stands at approximately (5~10)/1 million individuals. Notably, patients with malignant tumors exhibit an elevated risk of developing dermatomyositis compared to the general population. However, in cases where dermatomyositis co-occurs with malignancy, the efficacy of hormone therapy alone tends to be suboptimal. Moreover, reports addressing the correlation between tumor treatment and the management of dermatomyositis are scarce. A 60-year-old male patient presented with dermatomyositis, initially manifesting through symptoms such as rash, muscle weakness, and dysphagia. Despite undergoing standard hormone therapy, there was no discernible improvement in the dermatomyositis symptoms. Considering the patient's concomitant troublesome cough, further investigations were conducted, including CT, PET-CT, and pathological biopsy. These assessments confirmed the diagnosis of limited-stage small cell lung cancer (T1cN3M0 IIIB). Notably, in this patient, dermatomyositis was suspected to be a paraneoplastic syndrome associated with small cell lung cancer. Standard chemotherapy and radiotherapy were employed to treat the small cell lung cancer, resulting in partial remission after two treatment cycles. As the malignancy regressed, a notable improvement in dermatomyositis symptoms was observed, subsequently leading to a gradual reduction in the prescribed hormone dosage. In conclusion, we present a comprehensive case study of dermatomyositis as a paraneoplastic syndrome throughout the treatment process. The response to tumor therapy coincided with the amelioration of dermatomyositis symptoms. Therefore, diligent malignancy screening is imperative for patients diagnosed with dermatomyositis. [ABSTRACT FROM AUTHOR]

Immune checkpoint inhibitors have made remarkable breakthroughs in the treatment of lung cancer, bringing significant survival benefits to the patients. A number of adverse events aggravated by immunotherapy in patients with preexisting autoimmune diseases have been reported in the past, especially skin toxicity, such as rash, pruritus, erythema, and vitiligo. However, whether the exacerbated autoimmune disease is reversible and when it will return to its original state after immunotherapy discontinuation is still inconclusive. In our report, we described a patient diagnosed with non-small cell lung cancer whose vitiligo was stable for about 10 years. We followed up and observed the patient's skin depigmentation for the complete time window, from aggravation of application anti-programmed cell death-1 receptor antibody (anti-PD-1 antibody) to recovery after the withdrawal. We presented the objective images at particular time points using reflectance confocal microscopy and wood's light. We found that the use of anti-PD-1 antibody aggravated in skin toxicity, but it was reversible, the time window from the beginning to recovery status was approximately 9 months. We used this real case scenario to explain the relationships between immunotherapy and autoimmune diseases. [ABSTRACT FROM AUTHOR]

Lung cancer is the most fatal and frequently diagnosed malignant tumor. Neoadjuvant therapy is a promising approach for prolonging survival and increasing the chance of cure rates for patients with potentially resectable disease. Currently, many therapeutic alternatives, including chemotherapy, targeted therapy, and immunotherapy, are continually being explored to enrich the content of neoadjuvant therapy. However, neoadjuvant therapy remains to have no unified evaluation standards. Overall survival (OS) is the “gold standard” for evaluating the clinical benefit of cancer treatment, but it needs years for a reliable evaluation. Hence, researchers need to identify surrogate endpoints that can predict OS accurately and reliably without long follow-up periods. In this review, we describe the research progress of different neoadjuvant therapies and explore their response evaluation, aiming to identify stronger predictors of OS. [ABSTRACT FROM AUTHOR]

Background: The incidence of ocular metastasis from lung cancer is reported to be 0.1-7%, with adenocarcinoma and small cell lung cancer accounting for the highest proportions of these cases. The majority of cases involves metastasis to more than one other distal organ in addition to the eye. Here, we report for the first time, a case of lung squamous cell carcinoma with solitary symptomatic ocular metastasis as the initial manifestation that was managed by a multidisciplinary treatment (MDT).Case Presentation: A woman presented at the ophthalmology department of hospital with a 1-week history of left eye pain and blurred vision. Systemic examination led to the diagnosis of central lung cancer in the right lower lobe with ocular metastasis. After consultations with an MDT, including specialists from the surgery, internal medicine, ophthalmology, radiotherapy and imaging departments, the patient underwent surgery and chemotherapy. Her eye symptoms disappeared, and the ocular lesion was well controlled without any specific ocular treatment. The patient demonstrated a prolonged progression-free survival.Conclusion: This is the first report of a rare case with solitary ocular metastasis as the initial manifestation of lung squamous cell carcinoma. This rare patient was treated based on evidence-based medicine, indicating the importance of cooperation within an MDT. The successful treatment of this case was reported as a new therapeutic reference for clinicians who encounter similar cases in the future. [ABSTRACT FROM AUTHOR]

OBJECTIVES: This study aimed to examine the prognostic role of the plasma 25-hydroxyvitamin D (25(OH)D) level in advanced non-small cell lung cancer (NSCLC) patients treated with platinum-based doublet first-line chemotherapy. METHODS: A total of 195 advanced NSCLC patients were consecutively and prospectively hospitalized to receive platinumbased first-line chemotherapy. The baseline 25(OH)D level was measured at the time of diagnosis. Main outcome measures included overall survival (OS) and progression-free survival (PFS). RESULTS: With 10 ng/mL as the cutoff value for the baseline plasma 25(OH)D level, patients with 25(OH)D < 10 ng/mL (n = 54) and those with 25(OH)D ≥ 10 ng/mL (n = 141) were found to have similar characteristics in terms of age, sex, smoking status, pathological type, Eastern Cooperative Oncology Group (ECOG) performance status, and clinical staging (all P-values > 0.05). The median OS values of patients with 25(OH)D < 10 ng/mL and ≥ 10 ng/mL were 17.9 months (95% confidence interval [CI], 14.4-21.4 months) and 20.8 months (95%CI, 17.9-23.8 months), respectively; the median PFS values were 9.4 months (95%CI, 8.2-10.5 months) and 9.4 months (95%CI, 8.3-10.5 months), respectively. Both univariate and multivariate analyses showed that having a plasma 25(OH)D level < 10 ng/mL was associated with a significantly shorter OS (P = 0.003; P = 0.009), while the baseline plasma 25(OH)D level was not significantly associated with PFS. CONCLUSION: Deficiency of 25(OH)D is an independent prognostic factor for a poor OS in advanced NSCLC patients treated with platinum-based first-line chemotherapy. [ABSTRACT FROM AUTHOR]

Oncostatin M (OSM) is a cytokine of the interleukin-6 family and plays important roles during inflammation. However, its roles in myoblast differentiation and muscle regeneration remain unexplored. We show here that OSM potently inhibited myoblast differentiation mainly by activating the JAK1/STAT1/STAT3 pathway. OSM downregulated myocyte enhancer-binding factor 2A (MEF2A), upregulated the expression of Id1 and Id2, and inhibited the transcriptional activity of MyoD and MEF2. In addition, OSM also enhanced the expression of STAT3 and OSM receptor, which constituted a positive feedback loop to further amplify OSM-induced signaling. Moreover, we found that STAT1 physically associated with MEF2 and repressed its transcriptional activity, which could account for the OSM-mediated repression of MEF2. Although undetectable in normal muscles in vivo, OSM was rapidly induced on muscle injury and then promptly downregulated just before the majority of myoblasts differentiate. Prolonged expression of OSM in muscles compromised the regeneration process without affecting myoblast proliferation, suggesting that OSM functions to prevent proliferating myoblasts from premature differentiation during the early phase of muscle regeneration. [ABSTRACT FROM AUTHOR]

Background and Aim: Bmi-1 is a transcriptional repressor belonging to the Polycomb group and is associated with the cell proliferation and carcinogenesis of a variety of human cancers. The level of Bmi-1 expression correlates with the aggressiveness of many cancers, and is considered an important marker for cancer diagnosis. However, its role in gastric carcinoma is unknown. Methods: We used lentiviral mediated interfering short hairpin RNA to knockdown Bmi-1 expression in gastric carcinoma human gastric cancer cell line (AGS cells), then tested the cell proliferation by MTT assay, rate of colony formation by colony formation assay, cell cycle distribution by fluorescence-activated cell sorting and cell invasiveness by cell invasion assay. To analyze the expression and localization of Bmi-1 in gastric tumor tissues, we further performed the immunohistochemistry analysis on a gastric cancer tissue array. Results: We found that knocking down Bmi-1 led to slower cell growth, lesser cell invasiveness, decelerated colony formation, and altered cell cycle progression. In addition, a positive relationship between nuclear expression of Bmi-1 and gastric cancer was observed, suggesting that nucleus localization of Bmi-1 in the cells may be a novel marker of gastric cancer. Conclusions: Our study highlights critical roles for Bmi-1 in gastric cancer, and suggests that Bmi-1 nuclear localization could be an important marker for the diagnosis of gastric cancer. [ABSTRACT FROM AUTHOR]

We used two inhibitors of the signaling enzyme phosphatidylinositol 3-kinase (PtdIns3K), wortmannin and LY294002, to evaluate the potential involvement of PtdIns3K in the activation of the MAP kinases (MAPK), Erk1 and Erk2. In dose–response studies carried out on six different cell lines and a primary cell culture, we analyzed the ability of the inhibitors to block phosphorylation of protein kinase B/akt (PKB/akt) at Ser473 as a measure of PtdIns3K activity, or the phosphorylation of Erk1/2 at activating Thr/Tyr sites as a measure of the extent of activation of MAPK/Erk kinase (MEK/Erk). In three different hemopoietic cell lines stimulated with cytokines, and in HEK293 cells, stimulated with serum, either wortmannin or LY294002, but never both, could partially block phosphorylation of Erks. The same observations were made in a B-cell line and in primary fibroblasts. In only one cell type, the A20 B cells, was there a closer correlation between the PtdIns3K inhibition by both inhibitors, and their corresponding effects on Erk phosphorylation. However, this stands out as an exception that gives clues to the mechanism by which cross-talk might occur. In all other cells, acute activation of the pathway leading to Erk phosphorylation could proceed independently of PtdIns3K activation. In a biological assay comparing these two pathways, the ability of LY294002 and the MEK inhibitor, U0126, to induce apoptosis were tested. Whereas LY294002 caused death of cytokine-dependent hemopoietic cells, U0126 had little effect, but both inhibitors together had a synergistic effect. The data show that these two pathways are regulating very different downstream events involved in cell survival. [ABSTRACT FROM AUTHOR]

Myocyte enhancer factor 2 (MEF2) family proteins are key transcription factors controlling gene expression in myocytes, lymphocytes, and neurons. MEF2 proteins are known to be regulated by phosphorylation. We now provide evidence showing that MEF2C is acetylated by p300 both in vitro and in vivo. In C2C12 myogenic cells, MEF2 is preferentially acetylated in differentiating myocytes but not in undifferentiated myoblasts. Several major acetylation sites are mapped to the transactivation domain of MEF2C, some of which are fully conserved in other MEF2 members from several different species. Mutation of these lysines affects MEF2 DNA binding and transcriptional activity, as well as its synergistic effect with myogenin in myogenic conversion assays. When introduced into C2C12 myoblasts, the nonacetylatable MEF2C inhibits myogenic differentiation. Thus, in addition to phosphorylation, MEF2 activity is also critically regulated by acetylation during myogenesis. [ABSTRACT FROM AUTHOR]