ABSTRACT
Solitary fibrous tumors are typically benign and usually develop in the pleura. We herein report the first case of a solitary fibrous tumor that was pathologically malignant and developed in the left atrial endocardium. A 24-year-old woman underwent resection of a malignant solitary fibrous tumor in her right forearm at another hospital. Computed tomography demonstrated a mass in her right pleura 2 months after the surgery. She was referred to our hospital, and a tumor in her left atrium was subsequently found. She underwent resection of these tumors, and pathological examination showed that they were both malignant solitary fibrous tumors.
Subject(s)
Solitary Fibrous Tumor, Pleural , Solitary Fibrous Tumors , Adult , Endocardium/pathology , Female , Heart Atria/diagnostic imaging , Heart Atria/pathology , Heart Atria/surgery , Humans , Solitary Fibrous Tumors/diagnostic imaging , Solitary Fibrous Tumors/surgery , Tomography, X-Ray Computed , Treatment Outcome , Young AdultABSTRACT
This was a case of a woman in her 60s with the chief complaint of an abnormal stomach X-ray at the screening. Although suspected to be scirrhous gastric cancer, gastric biopsy revealed Group 1, and cytology in accumulated ascites and open surgery was initially Class II, but cancer cells in the ascites were confirmed for the first time by subsequent immunostaining using the cell transfer technique. Undifferentiated advanced gastric cancer, peritoneal dissemination, and lymphatic metastasis were pathologically observed. This case suggests the effectiveness of immunostaining when the results of ascites cytology are different from the clinical picture.
Subject(s)
Peritoneal Neoplasms , Stomach Neoplasms , Ascites/etiology , Female , Humans , Lymphatic Metastasis , Peritoneal Neoplasms/diagnostic imaging , Stomach Neoplasms/diagnostic imaging , Stomach Neoplasms/surgeryABSTRACT
INTRODUCTION: Estrogen receptors (ER) (ERα, ERß) and aromatase (key enzyme for estrogen synthesis) are expressed in most human NSCLCs. High intratumoral estrogen levels and elevated aromatase expression in NSCLC predict poor outcome. This open-label, phase 1b, single-center study evaluated the safety and tolerability of escalating doses of the aromatase inhibitor, exemestane, in combination with carboplatin and pemetrexed in postmenopausal women with stage IV nonsquamous NSCLC. METHODS: Patients received exemestane (starting 1-wk before chemotherapy) at 25 mg orally (PO) daily (cohort 1) or 50 mg PO daily (cohort 2) combined with carboplatin (area under the curve 6 mg × min/mL) and pemetrexed (500 mg/m2) intravenously every 3 weeks for four cycles. Thereafter, patients were eligible for continued therapy with exemestane and pemetrexed or pemetrexed alone. RESULTS: A total of 10 patients consented for therapy, and two patients failed in the screening. Four patients completed the therapy in cohort 1 and four patients in cohort 2. The median number of cycles administered was 15 (range: 1-54). Maximum tolerated dose was exemestane 50 mg PO daily with combination chemotherapy. Intention-to-treat analysis revealed an objective response rate (ORR) of 62.5% (five of eight patients with partial response) and a clinical benefit rate of 87.5% (seven of eight patients with either stable disease or partial response). ORR was associated with aromatase expression (p = 0.02). Circulating estrogen levels decreased with exemestane use, and quality of life measurements did not significantly change during the treatment. There were no adverse events. CONCLUSIONS: The combination of carboplatin, pemetrexed, and exemestane in postmenopausal women with metastatic NSCLC is safe and well tolerated. Biomarker studies revealed that ORR correlates with tumor aromatase expression. These findings support future clinical trials to confirm the antitumor efficacy with this combination therapy.
ABSTRACT
Sporadic inclusion body myositis (sIBM) is a degenerative, intractable, inflammatory myopathy with an immune pathomechanism. We report on a case of a 44-year-old Japanese man who began developing progressive muscle weakness at age 40. Rheumatoid arthritis symptoms manifested at 43 with strongly positive anti-cyclic citrullinated peptide antibodies. Along with typical sIBM pathology, a muscle biopsy revealed dramatic inflammation with prominent perivascular B-cell infiltration forming ectopic lymphoid follicle-like structures (ELFLSs). Exome sequencing identified no causative variants of hereditary myopathy or immune disorders. A combination of immunotherapy slowed the progression of the muscular symptoms. This unusual form of sIBM, including earlier age at onset, a partial response to immunotherapy, and a histopathology presenting B-cell infiltrate with ectopic lymphoid follicle-like structures, indicates a possible association of rheumatoid arthritis and heterogeneity with the autoimmune involvement of sIBM. We review the clinical and pathological features of patients with rheumatoid arthritis associated sIBM in the literature.
Subject(s)
Arthritis, Rheumatoid/diagnosis , Myositis, Inclusion Body/diagnosis , Tertiary Lymphoid Structures/etiology , Adult , Aged , Biopsy , Female , Humans , Male , Middle AgedABSTRACT
BACKGROUND: Bronchopulmonary dysplasia (BPD) is a chronic respiratory disease that occurs in premature infants and the prognosis is variable depending on the comorbidities including fibrosis, emphysema, or pulmonary hypertension (PH). We present a case of a 9-year-old girl who developed PH associated with severe BPD (BPD-PH) and underwent bilateral lung transplantation (BLTx). Case description A 9-year-old girl was admitted to our department to undergo BLTx. She was born at 23 weeks and 4 days gestation with a weight of 507 g. She received ventilation for the first 2 months and required further respiratory care due to repetitive, severe respiratory infections. She was diagnosed with BPD-PH at 6 months of age and oral administration of pulmonary vasodilators were initiated. She was registered as a lung transplant candidate at 4 years of age after the life-threatening exacerbation. Chest computed tomography (CT) revealed severe lung conditions with ground-glass opacities and emphysematous low-density areas in the upper and lower lobes. BLTx from a brain-dead male donor was performed. The pathological findings of her resected lung revealed saccular, hypoplastic lung with alveolar repair/regeneration, and medial hypertrophy and muscularization of peripheral arteries. The postoperative course was mostly uneventful. She was free from oxygen administration and showed no signs of PH after 6 months of the surgery. CONCLUSION: This is the first case report of BLTx in a pediatric, irreversible BPD-PH patient with detailed pathohistological findings and clinical examination. Lung transplantation is one of the treatment options for severe BPD-PH.
Subject(s)
Bronchopulmonary Dysplasia , Hypertension, Pulmonary , Lung Transplantation , Bronchopulmonary Dysplasia/complications , Child , Female , Humans , Hypertension, Pulmonary/complications , Infant , Infant, Newborn , Infant, Premature , Lung , MaleABSTRACT
BACKGROUND: Danon disease is an X-linked dominant disorder with defects in the lysosome-associated membrane protein 2 (LAMP2) gene and is characterized histologically by intracellular autophagic vacuoles in skeletal and cardiac muscles. Cardiac magnetic resonance (CMR) T1 mapping potentially allows to differentiate intracellular and extracellular cardiac abnormalities with a combination of native T1 value and extracellular volume (ECV) fraction. CASE SUMMARY: We assessed CMR T1 mapping in two Danon disease patients (a 22-year-old man and his 48-year-old mother), who had a LAMP2 c.864G>A p. Val288Val mutation, and two blood relatives without Danon disease (his 47-year-old maternal aunt and 49-year-old father). The male patient underwent a left ventricular (LV) assist device implantation at 15 months after the image acquisition because he was inotrope dependent (INTERMACS profile 3) and had no noticeable psychological or musculoskeletal symptoms. His mother was in New York Heart Association Class II with mildly reduced LV ejection fraction (46%). The Danon group showed late gadolinium enhancement (LGE) in the anterior and posterolateral LV walls. In the interventricular wall, where evident LGE was not noted, the Danon group had high native T1 value, compared with the T1 value in the non-Danon group, and normal ECV fraction. Cardiac biopsy from the interventricular wall showed intracytoplasmic autophagic vacuoles, which are characteristics of Danon disease. DISCUSSION: This characteristic pattern of high native T1 and normal ECV fraction in the areas without LGE, which may reflect the existence of intracytoplasmic autophagic vacuoles, may support the differential diagnosis of Danon disease from other cardiomyopathies.
ABSTRACT
A 73-year-old woman with no history of disease was referred to our hospital with fatigue and joint pain. Screening blood test showed that her cancer antigen 15-3 (CA 15-3) serum level was elevated to 36.6 U/mL, and a contrast-enhanced computed tomography scan revealed a bladder tumor without metastasis. Cystoscopy showed a papillary and a small kissing tumor, and the histopathological analysis of the bladder tumor obtained by transurethral resection (TUR) showed invasive urothelial carcinoma (UC) with micropapillary variant (pT1). At 4 weeks after TUR, the CA 15-3 serum level was markedly increased to 180.6 U/mL, and radiographic examinations revealed multiple regional and nonregional lymph node metastases. The patient received systemic therapy with gemcitabine and cisplatin. After 3 cycles of chemotherapy, the size of all lymph node metastases reduced by 80% in diameter, and the CA 15-3 serum level decreased from 238.2 to 11.4 U/mL. Immunohistological analysis showed that the bladder tumor was positive for mucin 1, of which CA 15-3 is an epitope. In our patient, changes in the CA 15-3 serum levels were in congruence with the clinical course of advanced micropapillary UC (MPUC). Therefore, the CA 15-3 serum level may be a potentially valuable biomarker for MPUC.
ABSTRACT
BACKGROUND/AIM: Acquired resistance to epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) has posed serious clinical problems in the treatment of lung adenocarcinoma (LADC) patients harboring relevant EGFR mutations. In this study, we explored the role of estrogen receptor ß (ERß) in the development of acquired resistance to EGFR-TKIs in human LADC. MATERIALS AND METHODS: First, the role of ERß in erlotinib resistance of LADC cell lines (PC9/ER) was examined. Then, the immunolocalization of ERß in 28 LADC patient samples treated with EGFR-TKIs was investigated. RESULTS: Cytoplasmic ERß was upregulated in erlotinib resistant cell lines. EGFR-TKIs sensitivity increased with ERß inhibition in PC9/ER cells. ERK1/2 and AKT activities were both markedly increased by specific ERß agonists even under erlotinib treatment of PC9/ER cells. Cytoplasmic ERß immunoreactivity was significantly associated with clinical response to EGFR-TKIs. CONCLUSION: Cytoplasmic ERß in LADC cells was involved in the development of resistance to EGFR-TKIs.
Subject(s)
Adenocarcinoma/genetics , Drug Resistance, Neoplasm/genetics , ErbB Receptors/antagonists & inhibitors , Erlotinib Hydrochloride/pharmacology , Estrogen Receptor beta/genetics , Lung Neoplasms/genetics , A549 Cells , Adenocarcinoma/metabolism , Adenocarcinoma/pathology , Cell Line, Tumor , Cell Survival/drug effects , Cell Survival/genetics , ErbB Receptors/genetics , ErbB Receptors/metabolism , Estradiol/pharmacology , Estrogen Receptor beta/metabolism , Estrogens/pharmacology , Gene Expression Regulation, Neoplastic/drug effects , Humans , Lung Neoplasms/metabolism , Lung Neoplasms/pathology , Protein Kinase Inhibitors/pharmacology , RNA InterferenceABSTRACT
Small tumor cell nests such as micropapillary nests are histologic poor prognostic markers for adenocarcinomas of various organs, including the lung. However, for the lung, the association of micropapillary patterns with smoking is controversial, which may be because of a vague definition of micropapillary patterns. This study clarifies the implications of small tumor cell nests by introducing a new dichotomic classification based on the glandular polarity of tumor cells: pure micropapillary nests (pMPs), preserving glandular polarity, and small solid nests (SSNs), lacking polarity. We examined the clinicopathologic factors in 436 resected adenocarcinomas, and analyzed the overall survival between groups classified by either the presence or absence of pMPs and SSNs. pMP was positively associated with nonsmoking-related features such as epidermal growth factor receptor mutations and thyroid transcription factor 1 expression. By contrast, SSN was positively associated with smoking-related features such as KRAS mutations and hepatocyte nuclear factor-4a expressions. Besides, pMP and SSN were significant and independent indicators of poor prognosis in all stages. SSN was an indicator in stage I too, whereas pMP was not. Furthermore, prognoses of the group with SSN were significantly worse than those of pMP-only group. In conclusion, the present study has revealed 2 completely different patterns of small tumor cell nests in lung adenocarcinoma, the nonsmoking-related pMPs, and the smoking-related SSNs, by considering glandular polarity. MPP should include only pMPs, and SSNs should be in a solid pattern. This novel classification might boast clinical significance as a potent poor prognostic marker as well as a factor reflecting etiological and genetic characters.
Subject(s)
Adenocarcinoma of Lung/pathology , Lung Neoplasms/pathology , Adenocarcinoma of Lung/etiology , Adenocarcinoma of Lung/mortality , Adenocarcinoma of Lung/surgery , Aged , Biomarkers, Tumor/analysis , Biomarkers, Tumor/genetics , Female , Genetic Predisposition to Disease , Humans , Lung Neoplasms/etiology , Lung Neoplasms/mortality , Lung Neoplasms/surgery , Male , Middle Aged , Mutation , Neoplasm Staging , Pneumonectomy , Retrospective Studies , Risk Assessment , Risk Factors , Smoking/adverse effects , Time Factors , Treatment OutcomeABSTRACT
OBJECTIVES: Metabolic tumor volume (MTV) on 18F-fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) is a promising prognostic predictor in pancreatic ductal adenocarcinoma (PDAC). However, the optimal segmentation method and threshold value to determine MTV for PDAC are still unclear. We explored the optimal method and threshold value for the prognostic value of MTV measured on pre-treatment 18F-FDG-PET/CT. METHODS: Seventy-three patients with resected PDAC who underwent 18F FDG-PET/CT before surgical resection were enrolled. MTV values of the tumor were measured on FDG-PET/CT by the two fixed-threshold methods using threshold values as 2.0, 2.5, 3.0, and 3.5 for the absolute method and 35%, 40%, 42%, 45%, and 50% for the relative method. Receiver operating characteristic curve analysis for prediction of 1-year survival rates was conducted for determining the optimal threshold values, and we selected the optimal method and threshold value considering area under the curve. The prognostic values of each FDG-PET/CT parameter for disease-specific survival and recurrence-free survival were assessed with Kaplan-Meier method and Cox proportional hazard models. RESULTS: In receiver operating characteristic curve analysis, MTV by the fixed-absolute threshold method based on a threshold value of 3.5 (MTV3.5) performed best in our study with area under the curve 0.724, sensitivity of 65%, and specificity of 75%. In univariate and multivariate analyses, MTV3.5 was significantly associated with disease-specific and recurrence-free survival. CONCLUSIONS: MTV3.5 by absolute threshold on pre-treatment FDG-PET/CT was the best independent prognostic predictor in resectable PDAC compared with other absolute threshold values and relative threshold values.
Subject(s)
Germ-Line Mutation/genetics , Osteosarcoma/genetics , Tuberous Sclerosis Complex 2 Protein/genetics , Tuberous Sclerosis/genetics , Tumor Suppressor Protein p53/genetics , Angiofibroma/complications , Angiomyolipoma/complications , Astrocytoma/complications , Child , Female , Humans , Mutation, Missense/genetics , Osteosarcoma/drug therapyABSTRACT
A woman in her 30s, who was clinically diagnosed with tuberous sclerosis complex, underwent lung transplantation due to lymphangioleiomyomatosis with concomitant multifocal micronodular pneumocyte hyperplasia (MMPH). Histologically, MMPH lesions demonstrated variety in histology; some showed homogenous cells with mild nuclear atypia and elastic fibers proliferation, and the others showed enlarged nuclei without elastic fibers. Because the natural history of MMPH is not well characterized, we used next-generation sequencing to perform a comprehensive genetic analysis for the MMPH lesions to explore their malignant potential. Regardless of their histological variety, three of four lesions had BRAF missense mutations, especially the types frequently detected in atypical adenomatous hyperplasia that is considered to be benign rather than a precursor of adenocarcinoma. None of them had major driver mutations of lung adenocarcinoma, except for BRAF mutations. In conclusion, our study of the lesions from this patient indicated the benign characteristic of MMPH.
Subject(s)
Alveolar Epithelial Cells/pathology , DNA Mutational Analysis , High-Throughput Nucleotide Sequencing , Lung Diseases/genetics , Mutation, Missense , Proto-Oncogene Proteins B-raf/genetics , Tuberous Sclerosis/genetics , Adult , Female , Genetic Predisposition to Disease , Humans , Hyperplasia , Lung Diseases/pathology , Lung Diseases/surgery , Lung Transplantation , Phenotype , Predictive Value of Tests , Tuberous Sclerosis/pathology , Tuberous Sclerosis/surgeryABSTRACT
BACKGROUND: The present study aimed to investigate the correlation between preoperative 2-deoxy-2-[18F]fluoro-d-glucose (18F-FDG) PET/CT findings and short-term survival in lung cancer patients with idiopathic interstitial pneumonia (IIP). METHODS: We retrospectively reviewed the data of 425 patients who underwent lung resection for non-small cell lung cancer without preoperative radiation therapy between November 2012 and October 2017. The maximum SUV (SUVmax) in the IIP area except the lung cancer site was measured in each patient. RESULTS: Thirty-one of the 425 patients (7.3%) showed findings of IIP in chest CT. Five of the 31 patients (16.1%) developed acute exacerbation (AE) after lung resection (AE+ group). Twenty-six of the 31 patients (83.9%) did not develop AE (AE- group). In the AE+ group, 18F-FDG SUVmax in the IIP area was significantly higher (1.9 ± 0.6 vs. 2.7 ± 0.7, p = 0.02) compared with that in the AE- group. The receiver operating characteristic analysis identified an SUVmax threshold score of 2.55 (p = 0.02) for AE. There was no 90-day mortality in the patients with SUVmax < 2.55 (n = 25). On the other hand, the 90-day mortality rate in patients with SUVmax ≥ 2.55 (n = 6) was 33.3% (2 patients). CONCLUSIONS: 18F-FDG PET/CT may predict AE after lung resection and could be related to short-term survival in lung cancer patients with IIP. Further investigations are needed to improve the prognosis in patients with high SUVmax in the IIP area.
Subject(s)
Carcinoma, Non-Small-Cell Lung/diagnostic imaging , Carcinoma, Non-Small-Cell Lung/surgery , Fluorodeoxyglucose F18 , Idiopathic Interstitial Pneumonias/complications , Idiopathic Interstitial Pneumonias/diagnostic imaging , Lung Neoplasms/diagnostic imaging , Lung Neoplasms/surgery , Pneumonectomy , Positron Emission Tomography Computed Tomography , Aged , Aged, 80 and over , Carcinoma, Non-Small-Cell Lung/complications , Carcinoma, Non-Small-Cell Lung/mortality , Female , Humans , Idiopathic Interstitial Pneumonias/mortality , Lung Neoplasms/complications , Lung Neoplasms/mortality , Male , Middle Aged , Postoperative Period , Preoperative Period , Prognosis , Survival Rate , Time FactorsABSTRACT
Immunotherapy is considered one of the most important therapeutic strategies for patients with lung adenocarcinoma after the development of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) resistance. However, useful predictors of immunotherapy for these patients has not been examined well, although the status of the tumor immune microenvironment (TIME), including programmed death-ligand 1 expression and lymphocyte infiltration, has been generally known to provide predictive markers for the efficacy of immunotherapy. This study aimed to clarify novel predictors of immunotherapy following EGFR-TKI resistance in lung adenocarcinoma, especially regarding micro RNA (miRNA). We evaluated the correlation between EGFR-TKI resistance and lymphocyte infiltration, before and after acquiring EGFR-TKI resistance, in 21 cases of lung adenocarcinoma, and further explored this by in vitro studies, using miRNA PCR arrays. Subsequently, we transfected miRNA-1 (miR-1), the most variable miRNA in this array, into three kinds of lung cancer cells, and examined the effects of miR-1 on EGFR-TKI sensitivity, cytokine expression and lymphocyte migration. Histopathological examination demonstrated that infiltration levels of CD8-positive T cells were significantly decreased after development of EGFR-TKI resistance. In vitro studies revealed that miR-1 significantly inhibited EGFR-TKI effect and induction of cytokines, such as C-C motif chemokine ligand 5 and C-X-C motif chemokine ligand 10, causing inhibition of monocyte migration. These results indicate that the upregulated miR-1 might suppress the TIME, following development of EGFR-TKI resistance. Therefore, miR-1 could be a clinically useful marker to predict therapeutic efficacy of immunotherapy in lung adenocarcinoma patients with EGFR-TKI resistance.
Subject(s)
Adenocarcinoma of Lung/immunology , Drug Resistance, Neoplasm , Lung Neoplasms/immunology , MicroRNAs/genetics , Protein Kinase Inhibitors/pharmacology , Tumor Microenvironment/immunology , Adenocarcinoma of Lung/drug therapy , Adenocarcinoma of Lung/genetics , Adenocarcinoma of Lung/pathology , Aged , Aged, 80 and over , Biomarkers, Tumor/genetics , ErbB Receptors/antagonists & inhibitors , Female , Follow-Up Studies , Gene Expression Regulation, Neoplastic , Humans , Lung Neoplasms/drug therapy , Lung Neoplasms/genetics , Lung Neoplasms/pathology , Male , Middle Aged , Prognosis , Tumor Cells, CulturedSubject(s)
Cell Cycle Proteins/metabolism , Hemangioma, Capillary/pathology , Lung Diseases/complications , Lung/abnormalities , MicroRNAs/metabolism , Abnormalities, Multiple/pathology , Adolescent , Female , Humans , Hypertension, Pulmonary/pathology , Lung/pathology , Lung/physiopathology , Lung Diseases/pathologyABSTRACT
BACKGROUND: Understanding the status of intratumoural immune microenvironment is necessary to ensure the efficacy of immune-checkpoint (IC) blockade therapy. Cortisol plays pivotal roles in glucocorticoid interactions in the immune system. We examined the correlation between intratumourally synthesised cortisol through 11ß hydroxysteroid dehydrogenase (HSD) 1 and the immune microenvironment in non-small-cell lung carcinoma (NSCLC). METHODS: We correlated 11ßHSD1 immunoreactivity in 125 cases of NSCLC with the amount of intratumoural immune cells present, and 11ßHSD1 immunoreactivity with the efficacy of IC blockade therapy in 18 specimens of NSCLC patients. In vitro studies were performed to validate the immunohistochemical examination. RESULTS: 11ßHSD1 immunoreactivity showed a significant inverse correlation with the number of tumour-infiltrating lymphocytes and CD3- or CD8-positive T cells. 11ßHSD1 immunoreactivity tended to be inversely correlated with the clinical efficacy of the IC blockade therapy. In vitro studies revealed that 11ßHSD1 promoted the intratumoural synthesis of cortisol. This resulted in a decrease in cytokines and in the inhibition of monocyte migration. CONCLUSIONS: Our study is the first report clarifying the inhibitory effects of intratumourally synthesised cortisol through 11ßHSD1 on immune cell migration. We propose that the response to IC blockade therapy in NSCLC may be predicted by 11ßHSD1.
Subject(s)
11-beta-Hydroxysteroid Dehydrogenase Type 1/genetics , Biomarkers, Tumor/genetics , Carcinoma, Non-Small-Cell Lung/genetics , Immune Checkpoint Inhibitors/administration & dosage , Aged , Aged, 80 and over , CD8-Positive T-Lymphocytes/drug effects , CD8-Positive T-Lymphocytes/immunology , Carcinoma, Non-Small-Cell Lung/immunology , Carcinoma, Non-Small-Cell Lung/pathology , Carcinoma, Non-Small-Cell Lung/therapy , Female , Humans , Immune Checkpoint Inhibitors/immunology , Male , Middle Aged , Tumor Microenvironment/drug effectsABSTRACT
PAP is a rare disease characterized by the accumulation of surfactant materials in the alveolar spaces due to the imbalance of surfactant homeostasis (production and clearance). We herein report a case of an 8-year-old girl who developed PAP after BMT from her mother for the treatment of DBA. The anemia was improved by BMT; however, respiratory dysfunction due to graft-versus-host disease gradually progressed. She eventually underwent right single LDLLT from her mother when she was 14 years old. A pathological examination of the excised lung confirmed the finding of diffuse bronchiolitis obliterans and unexpectedly revealed widespread alveolar proteinosis. Interestingly, the GGO of her native left lung on chest X-ray was improved after LDLLT. We present the very unique clinical course of this patient and discuss the mechanisms underlying the development of PAP after BMT and its improvement after LDLLT from the same donor.
Subject(s)
Anemia, Diamond-Blackfan/therapy , Bone Marrow Transplantation/adverse effects , Living Donors , Lung Transplantation/methods , Pulmonary Alveolar Proteinosis/surgery , Adolescent , Anemia, Diamond-Blackfan/complications , Child , Female , Humans , Pulmonary Alveolar Proteinosis/diagnosis , Pulmonary Alveolar Proteinosis/etiologyABSTRACT
Progesterone receptor (PR) is expressed in a wide variety of human tissues, including both reproductive and non-reproductive tissues. Upon binding to the PR, progesterone can display several non-reproductive functions, including neurosteroid activity in the central nervous system, inhibition of smooth muscle contractile activity in the gastrointestinal tract, and regulating the development and maturation of the lung. PR exists as two major isoforms, PRA and PRB. Differential expression of these PR isoforms reportedly contributes to different biological activities of the hormone. However, the distribution of the PR isoforms in human tissues has remained virtually unexplored. In this study, we immunolocalized PR expression in various human tissues using PR (1294) specific antibody, which is capable of detecting both PRA and PRB, and PRB (250H11) specific antibody. Tissues from the uterus, ovary, breast, placenta, prostate, testis, cerebrum, cerebellum, pituitary, spinal cord, esophagus, stomach, small intestine, colon, pancreas, liver, kidney, urinary bladder, lung, heart, aorta, thymus, adrenal gland, thyroid, spleen, skin, and bone were examined in four different age groups (fetal, pediatric, young, and old) in male and female subjects. PR and PRB were detected in the nuclei of cells in the female reproductive system, in both the nuclei and cytoplasm of pituitary gland and pancreatic acinar cells, and only in the cytoplasm of cells in the testis, stomach, small intestine, colon, liver, kidney, urinary bladder, lung, adrenal gland, and skin. Of particular interest, total PRB expression overlapped with that of total PR expression in most tissues but was negative in the female fetal reproductive system. The findings indicate that progesterone could affect diverse human organs differently than from reproductive organs. These findings provide new insights into the novel biological roles of progesterone in non-reproductive organs.
Subject(s)
Receptors, Progesterone/metabolism , Tissue Distribution , Adolescent , Adult , Aged , Child , Child, Preschool , Female , Fetus/metabolism , Humans , Infant , Infant, Newborn , Male , Middle Aged , Pregnancy , Progesterone/genetics , Progesterone/metabolism , Protein Isoforms/metabolism , Receptors, Progesterone/classification , Receptors, Progesterone/genetics , Receptors, Progesterone/isolation & purification , Reproduction/genetics , Young AdultABSTRACT
A 66-year-old woman presented with upper abdominal pain and weakness in the limbs. She had bilateral uveitis and gastric ulcers. A neurological examination revealed tetraparesis and sensory disturbance in the right arm. A cerebrospinal fluid (CSF) examination showed polymorphonuclear pleocytosis with elevated pro-inflammatory cytokine levels. Magnetic resonance imaging showed brain lesions and a long spinal cord lesion. She was initially diagnosed with neuro-Behçet's disease and was treated with corticosteroids, resulting in no improvement. A gastric mucosa biopsy indicated T-cell lymphoma colocalizing with neutrophils. The cytokine-mediated neutrophilic inflammation probably caused characteristic CSF and histopathological features. It is noteworthy that T-cell lymphoma may present with CSF neutrophilic inflammation.
Subject(s)
Antineoplastic Agents/adverse effects , Antineoplastic Agents/therapeutic use , Inflammation/chemically induced , Lymphoma, T-Cell/complications , Lymphoma, T-Cell/drug therapy , Lymphoma, T-Cell/mortality , Neutrophils/drug effects , Spinal Cord Diseases/chemically induced , Aged , Fatal Outcome , Female , Humans , Lymphoma, T-Cell/physiopathology , Magnetic Resonance Imaging , MaleABSTRACT
Cancer-associated fibroblasts (CAFs) exert various effects upon biological behaviours of cancer. In this study, we examined the correlation of CAFs with the intra-tumoural immune system in the lung adenocarcinoma microenvironment. We studied 27 and 113 cases of lung adenocarcinoma tentatively as Cohorts 1 and 2, respectively. The patients in Cohort 1 received epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) for recurrent lung adenocarcinoma. -smooth muscle actin (-SMA), a surrogate marker for CAFs, was examined by immunohistochemistry. We then examined the effects of CAFs isolated from lung cancer tissues on programmed death ligand 1 (PD-L1) expression in lung adenocarcinoma cell lines. No significant associations were detected between -SMA status and the ratios of CD8/CD4 and Foxp3/CD8 in Cohort 1. However, -SMA status was significantly associated with PD-L1 status in both Cohorts 1 and 2. Conditioned medium of CAFs significantly induced PD-L1 expression in lung adenocarcinoma cell lines, A549, PC-9, and H1975. Among the cytokines examined by antibody array, C-X-C motif chemokine ligand 2 (CXCL2) increased PD-L1 mRNA expression in these cell lines. CXCL2 is therefore considered to have a potential to induce PD-L1 expression in lung adenocarcinoma cells as a result of an interaction between carcinoma cells and CAFs. These findings did firstly demonstrate that CAFs indirectly influenced tumour immunity through increasing PD-L1 expression in lung adenocarcinoma cells.