Review
Cardiac & Cardiovascular Systems
Krishnan Warrior, Daniel F. Dilling
Summary: Lymphangioleiomyomatosis (LAM) is a rare cystic lung disease with respiratory symptoms and extra-thoracic manifestations. Lung transplantation can improve the life quality of LAM patients with end-stage lung disease, but there are unique considerations and complications associated with LAM. This review provides an overview of evaluation, management, and outcomes for LAM patients undergoing lung transplantation.
JOURNAL OF HEART AND LUNG TRANSPLANTATION
(2023)
Article
Cardiac & Cardiovascular Systems
Krishnan Warrior, Lorriana E. Leard, Arun R. Nair, Cynthia J. Gries, Andrew J. Fisher, Simon R. Johnson, Francis X. McCormack, Daniel F. Dilling
Summary: There is significant variability in the use of mTOR inhibitors in LAM patients on the lung transplant waiting list worldwide. Our survey suggests favorable outcomes for those patients who continue mTOR inhibitor use up to the time of transplant.
RESPIRATORY MEDICINE
(2022)
Review
Cell Biology
Nandini Kundu, Marina K. Holz
Summary: Lymphangioleiomyomatosis (LAM) is a rare disease primarily metastasizing to the lung, affecting women and caused by somatic mutations in the TSC1 or TSC2 genes, with estrogen driving its development. LAM, like many cancers, is a heterogeneous disease characterized by dysregulated cell signaling pathways and a diverse composition of cells. This review focuses on the heterogeneity of LAM, its metastatic features, deregulated signaling mechanisms, and the tumor microenvironment, with the aim of developing new therapeutic strategies beyond Sirolimus.
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
(2023)
Review
Medicine, General & Internal
Clara Bernardelli, Anna Caretti, Elena Lesma
Summary: Chronic inflammatory lung diseases are characterized by altered lipids metabolism and mTORC1 deregulation, leading to pro-inflammatory and senescent phenotypes. LAM, a rare pulmonary disease, is driven by dysregulated lipid metabolism and mTORC1 inhibition, resulting in cystic remodeling and loss of lung function. Understanding the role of lipids in LAM pathogenesis may lead to the discovery of biomarkers and innovative therapeutic approaches.
FRONTIERS IN MEDICINE
(2023)
Article
Medicine, Research & Experimental
Carmen Herranz, Francesca Mateo, Alexandra Baiges, Gorka Ruiz de Garibay, Alexandra Junza, Simon R. Johnson, Suzanne Miller, Nadia Garcia, Jordi Capellades, Antonio Gomez, August Vidal, Luis Palomero, Roderic Espin, Ana Extremera, Eline Blommaert, Eva Revilla-Lopez, Berta Saez, Susana Gomez-Olles, Julio Ancochea, Claudia Valenzuela, Tamara Alonso, Piedad Ussetti, Rosalia Laporta, Antoni Xaubet, Jose A. Rodriguez-Portal, Ana Montes-Worboys, Carlos Machahua, Jaume Bordas, Javier A. Menendez, Josep M. Cruzado, Roser Guiteras, Christophe Bontoux, Concettina La Motta, Aleix Noguera-Castells, Mario Mancino, Enrique Lastra, Raul Rigo-Bonnin, Jose C. Perales, Francesc Vinals, Alvaro Lahiguera, Xiaohu Zhang, Daniel Cuadras, Coline H. M. van Moorsel, Joanne J. van der Vis, Marian J. R. Quanjel, Harilaos Filippakis, Razq Hakem, Chiara Gorrini, Marc Ferrer, Aslihan Ugun-Klusek, Ellen Billett, Elzbieta Radzikowska, Alvaro Casanova, Maria Molina-Molina, Antonio Roman, Oscar Yanes, Miquel A. Pujana
Summary: Inhibition of mTOR is the standard treatment for LAM, but its efficacy varies and some patients still experience declining lung function. The heterogeneous symptoms and lack of non-invasive tests make diagnosis and monitoring of LAM challenging. Monoamine-derived biomarkers may offer preclinical evidence for novel therapeutic approaches.
EMBO MOLECULAR MEDICINE
(2021)
Article
Immunology
S. Bos, L. J. De Sadeleer, J. Yserbyt, L. J. Dupont, L. Godinas, G. M. Verleden, L. J. Ceulemans, B. M. Vanaudenaerde, R. Vos
Summary: Among the lung transplant recipients included in this study, 13% received mTORi treatment, mostly due to renal insufficiency and malignancy. However, half of the patients discontinued mTORi therapy after experiencing adverse events or drug toxicity.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2021)
Article
Medicine, General & Internal
Ji Zhang, Dong Liu, Bingqing Yue, Le Ban, Min Zhou, Hongmei Wang, Jian Lv, Bo Wu, Zhenguo Zhai, Kai-Feng Xu, Wenhui Chen, Jingyu Chen
Summary: This study summarized the clinical data of 25 patients with pulmonary LAM who underwent lung transplantation at two hospitals in China between 2010 and 2018. The study highlighted the importance of lung transplantation for LAM patients in the Asian population and emphasized the need for further research on sirolimus use and LAM-related complications.
FRONTIERS IN MEDICINE
(2021)
Article
Biochemistry & Molecular Biology
Clara Bernardelli, Silvia Ancona, Melania Lazzari, Antonella Lettieri, Piera Selvaggio, Valentina Massa, Cristina Gervasini, Fabiano Di Marco, Raffaella Chiaramonte, Elena Lesma
Summary: This study examines the role of senescence in lymphangioleiomyomatosis (LAM), a rare disease characterized by the disruption of lung parenchyma. Through experiments on LAM cells and lung fibroblasts, the authors demonstrate the senescent features of LAM cells and their impact on neighboring cells. This finding provides important insights into the development and progression of LAM.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Pharmacology & Pharmacy
Pil Soo Sung, Ji Won Han, Changho Seo, Joseph Ahn, Soon Kyu Lee, Hee Chul Nam, Ho Joong Choi, Young Kyoung You, Jeong Won Jang, Jong Young Choi, Seung Kew Yoon
Summary: This study demonstrated that mTOR inhibitors can help preserve renal function in liver transplantation recipients, especially in patients with renal impairment, without serious adverse events. Regardless of the timing of initiation, a switch to mTOR inhibitors showed significant improvement in kidney function.
FRONTIERS IN PHARMACOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Jilly Frances Evans, Kseniya Obraztsova, Susan M. Lin, Vera P. Krymskaya
Summary: The study focuses on the mechanistic target of rapamycin (mTOR) and wingless-related integration site (Wnt) signal transduction networks and their impact on cancer, drug resistance, and stem cell exhaustion, as well as the lung disease lymphangioleiomyomatosis (LAM). The review highlights potential therapeutic approaches targeting these pathways.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Naim Al Mahi, Erik Y. Zhang, Susan Sherman, Jane J. Yu, Mario Medvedovic
Summary: The traditional CMap analysis using bulk disease tissue signatures lacks resolution for identifying effective therapeutic agents, while single-cell RNA-seq allows for construction of cell-specific disease signatures but lacks methods for CMaP analysis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Respiratory System
Sanghoon Park, Eun Joo Lee
Summary: Lymphangioleiomyomatosis (LAM) is a rare disease that mostly affects the lungs and leads to pulmonary and extra-pulmonary symptoms. The use of mTOR inhibitors has shown significant improvement in LAM management, but there are still many unresolved issues.
JOURNAL OF THORACIC DISEASE
(2023)
Article
Chemistry, Organic
Scott W. Niman, Roberta Buono, David A. . Fruman, Christopher D. Vanderwal
Summary: We designed and executed a rapid synthesis of a complex analogue of the immunosuppressive natural product brasilicardin A using our recently developed MHAT-initiated radical bicyclization. The synthesis delivered the targeted analogue in 17 steps in the longest linear sequence. However, the analogue showed no observable immunosuppressive activity, highlighting the importance of the structural and stereochemical elements of the natural core scaffold.
Article
Biochemistry & Molecular Biology
Mulin Liang, Hongxing Dang, Qinghe Li, Weiben Huang, Chengjun Liu
Summary: In the lung injury induced by hyperoxia, inhibiting the activation of the mTOR signaling pathway effectively reduces the expression of alpha-SMA. Only the mTORC1/2 dual inhibitor OSI-027 showed an anti-proliferative effect, alleviating hyperoxia-induced lung injury and fibrosis in SD rat pups.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)
Letter
Respiratory System
Julie Ng, Gustavo Pacheco-Rodriguez, Lesa Begley, Yvonne J. Huang, Sergio Poli, Mark A. Perrella, Ivan O. Rosas, Joel Moss, Souheil El-Chemaly
Summary: Patients with end-stage LAM have a distinct microbiome signature compared to those with end-stage chronic obstructive pulmonary disease, potentially providing new insights into the frequent respiratory infections seen in LAM patients.
RESPIRATORY RESEARCH
(2021)
Article
Cardiac & Cardiovascular Systems
Tsuyoshi Ueno, Motohiro Yamashita, Natsumi Yamashita, Masashi Uomoto, Osamu Kawamata, Yoshifumi Sano, Hidetoshi Inokawa, Shin Hirayama, Mikio Okazaki, Shinichi Toyooka
Summary: This study retrospectively analyzed the perioperative morbidity and mortality rates in 11 patients with advanced non-small cell lung cancer who underwent salvage lung resection after immune checkpoint inhibitor therapy. The results showed that salvage lung resection was well tolerated in these patients, but lymph node metastasis at the time of initial diagnosis may increase the difficulty of the surgery.
GENERAL THORACIC AND CARDIOVASCULAR SURGERY
(2022)
Article
Surgery
Kento Fujii, Shin Tanaka, Megumi Ishihara, Kei Matsubara, Kohei Hashimoto, Shuji Okahara, Kazuhiko Shien, Ken Suzawa, Kentaroh Miyoshi, Shinji Otani, Hiromasa Yamamoto, Mikio Okazaki, Seiichiro Sugimoto, Masaomi Yamane, Shinichi Toyooka
Summary: Living lung donors have a satisfactory long-term health-related quality of life after surgery, although some donors experience poorer physical, mental, and social health. Factors such as donor and recipient age, lung allocation score, and recipient death can affect the mental and social health of the donors. The study emphasizes the importance of informing potential donors about relevant risk factors and providing appropriate support for high-risk donors.
CLINICAL TRANSPLANTATION
(2023)
Article
Cardiac & Cardiovascular Systems
Kei Matsubara, Shinji Otani, Haruchika Yamamoto, Yasuaki Tomioka, Toshio Shiotani, Kentaroh Miyoshi, Mikio Okazaki, Seiichiro Sugimoto, Masaomi Yamane, Shinichi Toyooka
Summary: The prognostic nutrition index (PNI), calculated using serum albumin and total lymphocyte count, is an independent prognostic parameter in registered candidates for lung transplantation (LTx). Low PNI at registration is associated with worse prognosis and increased waitlist mortality. Age, idiopathic interstitial pneumonia, lung allocation score (LAS), and PNI are independent prognostic factors for waitlist mortality in LTx candidates.
GENERAL THORACIC AND CARDIOVASCULAR SURGERY
(2023)
Article
Surgery
Kentaro Nakata, Mikio Okazaki, Shinichi Kawana, Yujiro Kubo, Dai Shimizu, Shin Tanaka, Kohei Hashimoto, Ken Suzawa, Kazuhiko Shien, Kentaroh Miyoshi, Hiromasa Yamamoto, Seiichiro Sugimoto, Shinichi Toyooka
Summary: This study aimed to determine the levels of S100A8/A9 after lung transplantation (LTx) and evaluate their impact on overall survival (OS) and chronic lung allograft dysfunction (CLAD)-free survival. The results showed that S100A8/A9 levels were elevated in a time-dependent manner until 3 days after LTx. High S100A8/A9 levels were associated with lower survival rates and CLAD-free survival rates. Multivariate Cox regression analysis showed that high S100A8/A9 levels were a determinant of poor OS and poor CLAD-free survival. In patients with a low primary graft dysfunction grade (0-2), high S100A8/A9 levels were also a poor prognostic factor.
CLINICAL TRANSPLANTATION
(2023)
Article
Surgery
Yasuaki Tomioka, Shin Tanaka, Shinji Otani, Toshio Shiotani, Haruchika Yamamoto, Kentaroh Miyoshi, Mikio Okazaki, Seiichiro Sugimoto, Masaomi Yamane, Shinichi Toyooka
Summary: Although the performance of lung transplantation in the elderly has improved globally, the age limit for cadaveric transplantation in Japan remains at 60 years. We investigated the long-term outcomes of lung transplantation in the elderly in Japan.
Article
Multidisciplinary Sciences
Yasuaki Tomioka, Seiichiro Sugimoto, Haruchika Yamamoto, Shuta Tomida, Toshio Shiotani, Shin Tanaka, Kazuhiko Shien, Ken Suzawa, Kentaroh Miyoshi, Shinji Otani, Hiromasa Yamamoto, Mikio Okazaki, Masaomi Yamane, Shinichi Toyooka
Summary: This study investigated the association between single-nucleotide polymorphisms (SNPs) and renal dysfunction after lung transplantation (LT) using a Japanese-specific SNP array. The presence of certain SNPs was found to be significantly associated with changes in Delta eGFR. Pre-transplant identification of these SNPs may help predict the risk of renal dysfunction after LT and enable personalized medicine.
SCIENTIFIC REPORTS
(2023)
Article
Multidisciplinary Sciences
Toshio Shiotani, Seiichiro Sugimoto, Yasuaki Tomioka, Haruchika Yamamoto, Shin Tanaka, Kentaroh Miyoshi, Ken Suzawa, Kazuhiko Shien, Hiromasa Yamamoto, Mikio Okazaki, Shinichi Toyooka
Summary: miR-21 in the bloodstream shows potential value in diagnosing CLAD after bilateral LT.
Review
Respiratory System
Shinichi Kawana, Kentaroh Miyoshi, Shin Tanaka, Seiichiro Sugimoto, Dai Shimizu, Kei Matsubara, Mikio Okazaki, Noboru Hattori, Shinichi Toyooka
Summary: This study reports two cases of pulmonary alveolar proteinosis (PAP) after lung transplantation. One case involved a 4-year-old boy who died due to infection and was diagnosed with PAP at autopsy. The second case was a 52-year-old man who showed improvement with tapering immunosuppression. Transplant physicians should be aware of this rare complication to avoid misdiagnosis and improper immunosuppression management.
RESPIROLOGY CASE REPORTS
(2023)
Article
Oncology
Naoki Matsuda, Hiromasa Yamamoto, Tomohiro Habu, Kazuma Iwata, Kei Matsubara, Shin Tanaka, Kohei Hashimoto, Kazuhiko Shien, Ken Suzawa, Kentaroh Miyoshi, Tomohiro Toji, Mikio Okazaki, Seiichiro Sugimoto, Katsuhito Takahashi, Shinichi Toyooka
Summary: This study found that tumor-infiltrating lymphocytes (TILs), tertiary lymphoid structures (TLSs), and neutrophil-to-lymphocyte ratio (NLR) are closely associated with the prognosis of patients with pulmonary metastases from uterine leiomyosarcoma. Specifically, high expression of CD3-positive TILs, CD8-positive TILs, TLSs, and low NLR levels are correlated with better prognosis.
ANNALS OF SURGICAL ONCOLOGY
(2023)
Article
Surgery
Yujiro Kubo, Seiichiro Sugimoto, Toshio Shiotani, Kei Matsubara, Kohei Hashimoto, Shin Tanaka, Kazuhiko Shien, Ken Suzawa, Kentaroh Miyoshi, Hiromasa Yamamoto, Mikio Okazaki, Shinichi Toyooka
Summary: The percentage of low attenuation area (%LAA) on computed tomography (CT) is useful for evaluating lung emphysema and has been found to be higher in patients with chronic lung allograft dysfunction (CLAD) after bilateral lung transplantation (LT). This study investigated the relationship between %LAA and CLAD development. The results showed that %LAA was significantly higher in the CLAD group, especially in patients with bronchiolitis obliterans syndrome (BOS), and there were significant negative correlations between %LAA and baseline values of pulmonary function test parameters at the time of CLAD diagnosis.
CLINICAL TRANSPLANTATION
(2023)
Article
Surgery
Akikazu Hagiyama, Seiichiro Sugimoto, Shin Tanaka, Kei Matsubara, Kentaroh Miyoshi, Yoshimi Katayama, Masanori Hamada, Masuo Senda, Shinichi Toyooka
Summary: The association of changes in skeletal muscle mass and quality during the waiting time with outcomes of lung transplantation (LT) remains unclear. Maintaining or increasing skeletal muscle mass during the waiting time would be beneficial to improve the short-term outcomes of LT.
CLINICAL TRANSPLANTATION
(2023)
Article
Genetics & Heredity
Fumiaki Takatsu, Ken Suzawa, Shuta Tomida, Yin Min Thu, Masakiyo Sakaguchi, Tomohiro Toji, Masayoshi Ohki, Shimpei Tsudaka, Keiichi Date, Naoki Matsuda, Kazuma Iwata, Yidan Zhu, Kentaro Nakata, Kazuhiko Shien, Hiromasa Yamamoto, Akiko Nakayama, Mikio Okazaki, Seiichiro Sugimoto, Shinichi Toyooka
Summary: CAF-derived POSTN plays a crucial role in tumor growth, migration, EMT induction, and drug resistance in NSCLC. Targeting CAF-secreted POSTN could be a potential therapeutic strategy for NSCLC.
JOURNAL OF MOLECULAR MEDICINE-JMM
(2023)
Correction
Multidisciplinary Sciences
Yasuaki Tomioka, Seiichiro Sugimoto, Haruchika Yamamoto, Shuta Tomida, Toshio Shiotani, Shin Tanaka, Kazuhiko Shien, Ken Suzawa, Kentaroh Miyoshi, Shinji Otani, Hiromasa Yamamoto, Mikio Okazaki, Masaomi Yamane, Shinichi Toyooka
SCIENTIFIC REPORTS
(2023)
Article
Cardiac & Cardiovascular Systems
Mikio Okazaki, Ken Suzawa, Kazuhiko Shien, Hiromasa Yamamoto, Kota Araki, Mototsugu Watanabe, Masanori Okada, Yuho Maki, Tsuyoshi Ueno, Shinji Otani, Ryujiro Sugimoto, Hitoshi Nishikawa, Riki Okita, Makio Hayama, Hiroyuki Tao, Toshiya Fujiwara, Hidetoshi Inokawa, Yuji Hirami, Yoshifumi Sano, Motohiro Yamashita, Osamu Kawamata, Motoki Matsuura, Shinichi Toyooka
Summary: We retrospectively examined the surgical outcome and prognosis of ipsilateral anatomical resection for lung cancer after pulmonary lobectomy using a multicentre database. The 5-year overall survival rate after anatomical resection followed by ipsilateral lobectomy is comparable to that in patients who underwent anatomical resection without prior pulmonary lobectomy, but with a higher frequency of intraoperative and postoperative complications.
EUROPEAN JOURNAL OF CARDIO-THORACIC SURGERY
(2023)
