Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Therapeutic Targeting of Cancer-Associated Fibroblasts in the Non-Small Cell Lung Cancer Tumor Microenvironment

Lung cancer is the most frequently diagnosed cancer and the leading cause of cancer death worldwide. The most common lung cancer is non-small cell lung cancer (NSCLC), with an overall 5-year survival rate of around 20% because NSCLC is a metastatic disease. A better understanding of the mechanism underlying lung cancer metastasis is therefore urgently needed. The tumor microenvironment involves different types of stromal cells and functions as key components in the progression of NSCLC. Through epithelial–mesenchymal transition (EMT), in which epithelial cells lose their polarity and acquire mesenchymal potential, cancer cells acquire metastatic abilities, as well as cancer stem-cell-like potential. We previously reported that cancer-associated fibroblasts (CAFs) interact with lung cancer cells to allow for the acquisition of malignancy and treatment resistance by paracrine loops via EMT signals in the tumor microenvironment. Furthermore, CAFs regulate the cytotoxic activity of immune cells via various cytokines and chemokines, creating a microenvironment of immune tolerance. Regulation of CAFs can therefore affect immune responses. Recent research has shown several roles of CAFs in NSCLC tumorigenesis, owing to their heterogeneity, so molecular markers of CAFs should be elucidated to better classify tumor-promoting subtypes and facilitate the establishment of CAF-specific targeted therapies. CAF-targeted cancer treatments may suppress EMT and regulate the niche of cancer stem cells and the immunosuppressive network and thus may prove useful for NSCLC treatment through multiple mechanisms

Thoracoscopic segmentectomy for intralobar sequestration in adult: a case report

Abstract Background Surgical resection is the first choice for intralobar sequestration (ILS). A lobectomy is often performed, though we consider that a segmentectomy may be sufficient for benign cases if the sequestration is completely included within a segment. Case presentation We treated a 36-year-old female diagnosed with ILS. Chest computed tomography (CT) revealed several cystic lesions with niveau formation and consolidation in left segment (S)10 without communication of the bronchus and abnormal artery branching from the descending aorta. We performed a sublobar resection of left S10 including sequestration through a thoracoscopic minimally sized incision. The sequestration had dark red appearance and was completely included in the S10. The boundary line of S10 was clear with inflation of the lung after cutting bronchus 10. The postoperative course was uneventful. Chest CT findings at 2 years after surgery showed good expansion of the residual left lower lobe with no consolidation and respiratory function were nearly the same as the preoperative condition. Conclusions A thoracoscopic segmentectomy for ILS is a feasible and useful procedure for qualified cases, even in adult patients who had repeated inflammation

Nontuberculous mycobacterial infection after lung transplantation: a report of four cases

Abstract Background Nontuberculous mycobacterium (NTM) infection in a patient in an immunosuppressed state caused by increased use of immunosuppressive or biological agents is a serious clinical problem. Mycobacterium avium complex is the most common involved pathogen, followed by Mycobacterium abscessus (MABSC), while Mycobacterium kansasii is not a major concern. The rate of infection rate in lung transplant recipients is reported to range from 1.5–22.4%. Case presentation We report here four cases of NTM pulmonary infection and disease among 63 patients who underwent lung or heart-lung transplantation at our hospital. Those four occurred following living-donor transplantation in two patients, one with pulmonary arterial hypertension and one with bronchiectasia, and deceased donor lung transplantation in two patients, lymphangioleiomyomatosis and interstitial pneumonia, respectively. NTM was not detected in any of the patients prior to transplantation. The involved pathogens were Mycobacterium gordonae in one, MAC in one, and MABSC in two of these patients, which were isolated from broncho-alveolar lavage (BAL) in two and sputum in two. The one case of MAC and two of MABSC were symptomatic with consolidation shown in chest CT images indicating possible pneumonia, while the one with M. gordonae had no symptoms and was detected by surveillance BAL. Onset time from detection of NTM was greater than 3 years in the three with MABSC and M. gordonae and less than 3 years in the one with MAC. Each patient required a decrease in immunosuppressive agents according to their condition, while antibiotics therapy was performed in the three who were symptomatic. Sputum culture findings became negative after several months and were maintained thereafter in all. Conclusion An NTM infection leading to pulmonary disease can occur at any time following lung transplantation. Treatment should be considered depending on the involved pathogens, individual status, and disease severity

Significance of the Surgical Treatment with Lymph Node Dissection for Neuroendocrine Tumors of Thymus

Background: Neuroendocrine tumors of a thymus (NETTs) are rare, accounting for approximately 2–5% of all thymic epithelial tumors, and have a poor prognosis due to frequent lymph nodes or distant metastasis. Methods: We retrospectively reviewed the clinicopathological background and outcomes of 40 patients who underwent resection or surgical biopsy with histologically diagnosed NETTs from 1986 to 2022. Results: The most common pathological type was atypical carcinoid. Surgical resection was performed in 35 patients, with lymph node dissection in 33 and surgical biopsy in five. The overall survival (OS) rate for all patients was 81.4% and 52.3% at 5 and 10 years, respectively. The 2-year survival rate was 20% for the biopsy group, which was significantly worse than that of the resected group (p < 0.001). The relapse-free survival rates were 61.7% and 37.6% at 5 and 10 years, respectively, in 34 patients with complete resection. The univariate analysis revealed better the OS rate in the resected cases but with no significant differences between histological grade, lymph node metastasis, tumor size, or Ki67 index. Conclusions: Surgical complete resection is considered to improve prognosis regardless of histologic type. NETTs frequently develop lymph node metastasis, thus, lymph node dissection seems necessary for complete resection

Host Immune Response and Novel Diagnostic Approach to NTM Infections

The incidence and prevalence of non-tuberculous mycobacteria (NTM) infections are steadily increasing worldwide, partially due to the increased incidence of immunocompromised conditions, such as the post-transplantation state. The importance of proper diagnosis and management of NTM infection has been recently recognized. Host immunological responses play integral roles in vulnerability to NTM infections, and may contribute to the onset of specific types of NTM infection. Furthermore, distinct NTM species are known to affect and attenuate these host immune responses in unique manners. Therefore, host immune responses must be understood with respect to each causative NTM species. Here, we review innate, cellular-mediated, and humoral immunity to NTM and provide perspectives on novel diagnostic approaches regarding each NTM species

Two cases of lobectomy for lung cancer after transcatheter aortic valve implantation

Abstract Background The age of patients with lung cancer is advancing, and the number of patients with lung cancer who have cardiac diseases is expected to increase. Recently, the rate of transcatheter aortic valve implantation (TAVI) has increased as treatment for aortic stenosis (AS). TAVI is minimally invasive compared with conventional aortic valve replacement. We herein report two patients with lung cancer who underwent lobectomy after TAVI for severe AS. Case presentation Two patients with AS and lung cancer were treated with two-stage surgery of TAVI followed by lobectomy. In patient 1 (77 years of age), conventional aortic valve replacement was considered to be risky because of his history of coronary artery disease and thoracic aortic aneurysm and his relatively high logistic euroSCORE. He underwent TAVI followed by right middle and lower lobectomy. In patient 2 (75 years of age), TAVI was chosen because the patient had poor ADL due to spinal canal stenosis and had taken immunosuppressant agents after a kidney transplantation. He underwent TAVI followed by right lower lobectomy. The postoperative course of the two patients was uneventful. Conclusions Two-stage surgery of TAVI and lung resection could be a viable option for patients with both lung cancer and severe AS, for whom conventional AVR by an open-heart operation is not indicated