Chihiro Inoue

INTRODUCTION: Myelolipoma is a benign tumor composed of mature adipose tissue and hematopoietic elements that typically arises in the adrenal glands, and involvement of the anterior abdominal region is extremely uncommon. We report a rare case of myelolipoma arising in the subxiphoid preperitoneal region adjacent to the site where a sternum-lifting device had been placed during previous surgery.CASE PRESENTATION: A 62-year-old man had undergone extended thymectomy for thymoma associated with myasthenia gravis at the age of 39. The procedure was performed via bilateral video-assisted thoracoscopic surgery using a sternum-lifting technique. The tumor was classified as Masaoka stage III, and postoperative radiotherapy was administered. No recurrence was observed during 13 years of follow-up. Ten years after completion of follow-up, CT performed for an unrelated condition incidentally revealed a slowly enlarging 65 × 40-mm mass in the preperitoneal space, adjacent to the previous surgical site where a sternum-lifting device had been placed. MRI demonstrated a fat-containing component within the lesion, and the differential diagnosis included liposarcoma and teratoma. Complete surgical resection was therefore planned. A midline incision extending caudally from the xiphoid process was made, and en bloc resection of the tumor with the involved peritoneum was performed via laparotomy. Histopathological examination revealed mature adipose tissue admixed with hematopoietic elements, confirming the diagnosis of myelolipoma.CONCLUSIONS: This unique case of extra-adrenal myelolipoma highlights the importance of MRI-based qualitative assessment for tumors arising at unusual sites and underscores the need to include extra-adrenal myelolipoma in the differential diagnosis of fat-containing lesions occurring at previous surgical sites.

Lung adenocarcinoma (LUAD) associated with usual interstitial pneumonia (UIP) harbours distinct features compared to lung adenocarcinoma without UIP. Therefore, we aimed to characterise the tumour microenvironment of LUAD with UIP by focusing on cancer-associated fibroblasts (CAFs) and stromal composition. Immunohistochemistry was performed on 32 LUAD samples (16 each with and without UIP) to evaluate CAF marker expression and lymphocyte infiltration. Proteomic analysis of laser-microdissected stromal regions and reanalysis of publicly available single-cell RNA sequencing data were subsequently performed. LUAD with UIP had higher levels of podoplanin and collagen triple helix repeat containing 1 (CTHRC1) immunoreactivity, among the CAF markers examined in the fibrous stroma, increased inflammatory cell infiltration, and higher CD8 + and Foxp3 + lymphocyte counts than LUAD without UIP. The proteomic analysis revealed elevated aggrecan (ACAN) and hyaluronan and proteoglycan link protein 1 (HAPLN1) levels in the stroma of LUAD patients with UIP tissues, which was subsequently confirmed by immunohistochemistry. Single-cell RNA sequencing also supported ACAN and HAPLN1 expression in a subset of CAFs based on public data. The tumour microenvironment of LUAD in patients with UIP harbours distinct characteristics, including altered CAF markers and increased inflammatory cell infiltration in stromal components. Novel stromal proteins such as ACAN and HAPLN1 may play a role in the pathogenesis of LUAD with UIP.

Elucidating the mechanisms of action of steroid hormones will contribute to the development of therapeutic strategies for hormone-dependent tumors. Recent advances in genetic engineering have revealed the complex and diverse mechanisms of steroid hormone signaling; however, these techniques are limited to in vitro or animal experiments. It is believed that verifying hormone signals elucidated using human pathological tissue specimens will directly aid in treatment and diagnosis. However, pathological tissue specimens are generally formalin-fixed paraffin-embedded (FFPE), and protein/gene analyses of FFPE tissues are limited. Protein detection using immunohistochemistry with specific antibodies in FFPE tissues is a classical technique essential for diagnosis and treatment decisions in various types of cancer. In steroid hormone signaling, the expression and localization of receptors, hormone-related enzymes, and proteins encoded by response genes can be clarified using immunohistochemistry. Although protein-protein interactions such as receptor dimers and DNA-binding proteins are mainly detected in vitro, they can be examined in FFPE tissues using in situ proximity ligation assays and southwestern histochemistry, respectively. Using these detection methods, including immunohistochemistry, it is possible to analyze each hormone signaling pathway in hormone-related tumors histopathologically. Although FFPE tissues still suffer from gene and protein denaturation, their advantages include the ability to retrospectively study target factors/signals and obtain spatial information through microscopy. This review describes a visualization method for elucidating steroid hormone signaling in hormone-dependent tumors using FFPE tissues.

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The importance of sex hormones, especially estrogen, in the pathogenesis of non-small-cell lung cancer (NSCLC) has attracted attention due to its high incidence among young adults and nonsmokers, especially those who are female. Cancer-associated fibroblasts (CAFs) reside in the cancer stroma and influence cancer growth, invasion, metastasis, and acquisition of drug resistance through interactions with cancer cells and other microenvironmental components. Hormone-mediated cell–cell interactions are classic cell–cell interactions and well-known phenomena in breast cancer and prostate cancer CAFs. In cancers of other organs, including NSCLC, the effects of CAFs on hormone-receptor expression and hormone production in cancer tissues have been reported; however, there are few such studies. Many more studies have been performed on breast and prostate cancers. Recent advances in technology, particularly single-cell analysis techniques, have led to significant advances in the classification and function of CAFs. However, the importance of sex hormones in cell–cell interactions of CAFs in NSCLC remains unclear. This review summarizes reports on CAFs in NSCLC and sex hormones in cancer and immune cells surrounding CAFs. Furthermore, we discuss the prospects of sex-hormone research involving CAFs in NSCLC.

The presence of progesterone receptor (PR) and PR isoform B (PRB) in breast cancer is generally correlated with better clinical outcomes. Additionally, the significance of hormone-independent effects of PR/PRB correlated with better prognosis have been reported in non-small lung cancer (NSCLC). However, the detailed mechanism of that still remains unclear. In this study, we examined how microRNAs (miRNAs) could contribute to tumor inhibition via PR/PRB expression, in order to find miRNAs that have tumor-agnostic effects between breast cancer and NSCLC. We obtained miRNAs data using human tissues of breast cancer and NSCLC from The Cancer Genome Atlas database and PCR array from NSCLC patients of our cohort. Subsequently, we examined the function of the miRNA through in vitro study using breast cancer cell lines. As a result, only let-7b expression was significantly correlated with PR expression in both cancers. Additionally, the expression of let-7b significantly inhibited cell proliferation by inducing PR and PRB expression in breast cancer cell lines. However, the positive correlation of let-7b and PRB required a mediated factor, E2F1, obtained from TGCA databases analysis. In vitro experiments showed that let-7b significantly inhibited E2F1, and E2F1 significantly inhibited PRB. This study revealed that PRB inhibits the proliferation of breast cancer cells by the let-7b-E2F1 interaction. In addition, the immunohistochemical analysis in NSCLC was also consistent with these in vitro data. Our results could contribute to developing novel therapeutic strategies for patients with PR/PRB-positive cancer by targeting let7b or PRB expression in breast cancer and possibly NSCLC.

Background: Indium lung is characterized by interstitial pneumonia and/or emphysema which occurs in indium-tin oxide (ITO) workers. Indium lung is now known to progress after stopping exposure to ITO, but the long-term influences of ITO remain unclear. Case presentation: Forty seven years old, a never-smoker, who had been engaged in an ITO manufacturing process for 8 years. Emphysema was indicated by the medical check-up for ex-ITO workers, and he was diagnosed with indium lung. He underwent partial lung resections for pneumothorax two times, and obstructive pulmonary dysfunction had progressed through the years. He underwent right single lung transplant 20 years after ITO exposure. Pathologically, his lung showed severe distal acinar emphysema and honeycomb change. Fibrosis and destruction of the lung tissue significantly progressed compared to the previous partial resections. Scanning electron microscopy combined with energy dispersive spectroscopy revealed that the deposited particles contained indium and tin. After the transplantation, his respiratory function was improved. Conclusions: In this case, ITO resided in the lung tissue for 20 years, and lung tissue destruction kept progressing. Careful medical follow-up is recommended for ITO-workers even if they are asymptomatic.

As shown in our previous studies, the intratracheal-administration of STC1 (stanniocalcin-1) ameliorates pulmonary fibrosis by reducing oxidative and endoplasmic reticulum stress through the uncoupling of respiration in a bleomycin-treated mouse model. However, the overall effect of STC1 on metabolism was not examined. Therefore, we first conducted a comprehensive metabolomics analysis to screen the overall metabolic changes induced by STC1 in an alveolar epithelial cell line using capillary electrophoresis time-of-flight mass spectrometry. The results were subsequently validated in multiple alveolar epithelial and fibroblast cell lines by performing precise analyses of each substance. STC1 stimulated glycolysis, acetyl-CoA synthesis, and the methionine and cysteine-glutathione pathways, which are closely related to the uncoupling of respiration, modulation of epigenetics, and reduction in oxidative stress. These results are consistent with our previous study. Subsequently, we focused on the inhibitory factor SMAD7, which exerts an antifibrotic effect and is susceptible to epigenetic regulation. STC1 upregulates SMAD7 in an uncoupling protein 2–dependent manner, induces demethylation of the SMAD7 promoter region and acetylation of the SMAD7 protein in human alveolar epithelial and fibroblast cell lines and a bleomycin-treated mouse model, and subsequently attenuates fibrosis. The antifibrotic effects of STC1 may partially depend on the regulation of SMAD7. In the evaluation using lung tissue from patients with idiopathic pulmonary fibrosis, SMAD7 expression and acetylation were high in the alveolar structure-preserving region and low in the fibrotic region. The intratracheal administration of STC1 may prevent the development of pulmonary fibrosis by regulating the metabolism-mediated epigenetic modification of SMAD7 in patients.