The single-cell transcriptional landscape of lung carcinoid tumors

Lung carcinoid tumors, also referred to as pulmonary neuroendocrine tumors or lung carcinoids, are rare neoplasms of the lung with a more favorable prognosis than other subtypes of lung cancer. Still, some patients suffer from relapsed disease and metastatic spread while no consensus treatment exists for metastasized carcinoids. Several recent single-cell studies have provided detailed insights into the cellular heterogeneity of more common lung cancers, such as adeno- and squamous cell carcinoma. However, the characteristics of lung carcinoids on the single-cell level are yet completely unknown. To study the cellular composition and single-cell gene expression profiles in lung carcinoids, we applied single-cell RNA sequencing to three lung carcinoid tumor samples and normal lung tissue. The single-cell transcriptomes of carcinoid tumor cells reflected intertumoral heterogeneity associated with clinicopathological features, such as tumor necrosis and proliferation index. The immune microenvironment was specifically enriched in non- inflammatory monocyte-derived myeloid cells. Tumor-associated endothelial cells were characterized by distinct gene expression profiles. A spectrum of vascular smooth muscle cells and pericytes predominated the stromal microenvironment. We found a small proportion of myofibroblasts exhibiting features reminiscent of cancer-associated fibroblasts. Stromal and immune cells exhibited potential paracrine interactions which may shape the microenvironment via NOTCH, VEGF, TGFβ and JAK/STAT signaling. Moreover, single-cell gene signatures of pericytes and myofibroblasts demonstrated prognostic value in bulk gene expression data. Here, we provide first comprehensive insights into the cellular composition and single-cell gene expression profiles in lung carcinoids, demonstrating the non-inflammatory and vessel-rich nature of their tumor microenvironment, and outlining relevant intercellular interactions which could serve as future therapeutic targets

The single-cell transcriptional landscape of lung carcinoid tumors

Lung carcinoid tumors, also referred to as pulmonary neuroendocrine tumors or lung carcinoids, are rare neoplasms of the lung with a more favorable prognosis than other subtypes of lung cancer. Still, some patients suffer from relapsed disease and metastatic spread. Several recent single-cell studies have provided detailed insights into the cellular heterogeneity of more common lung cancers, such as adeno- and squamous cell carcinoma. However, the characteristics of lung carcinoids on the single-cell level are yet completely unknown. To study the cellular composition and single-cell gene expression profiles in lung carcinoids, we applied single-cell RNA sequencing to three lung carcinoid tumor samples and normal lung tissue. The single-cell transcriptomes of carcinoid tumor cells reflected intertumoral heterogeneity associated with clinicopathological features, such as tumor necrosis and proliferation index. The immune microenvironment was specifically enriched in non-inflammatory monocyte-derived myeloid cells. Tumor-associated endothelial cells were characterized by distinct gene expression profiles. A spectrum of vascular smooth muscle cells and pericytes predominated the stromal microenvironment. We found a small proportion of myofibroblasts exhibiting features reminiscent of cancer-associated fibroblasts. Stromal and immune cells exhibited potential paracrine interactions which may shape the microenvironment via NOTCH, VEGF, TGFβ and JAK/STAT signaling. Moreover, single-cell gene signatures of pericytes and myofibroblasts demonstrated prognostic value in bulk gene expression data. Here, we provide first comprehensive insights into the cellular composition and single-cell gene expression profiles in lung carcinoids, demonstrating the non-inflammatory and vessel-rich nature of their tumor microenvironment, and outlining relevant intercellular interactions which could serve as future therapeutic targets

Single-cell RNA sequencing reveals distinct tumor microenvironmental patterns in lung adenocarcinoma

Recent developments in immuno-oncology demonstrate that not only cancer cells, but also the tumor microenvironment can guide precision medicine. A comprehensive and in-depth characterization of the tumor microenvironment is challenging since its cell populations are diverse and can be important even if scarce. To identify clinically relevant microenvironmental and cancer features, we applied single-cell RNA sequencing to ten human lung adenocarcinomas and ten normal control tissues. Our analyses revealed heterogeneous carcinoma cell transcriptomes reflecting histological grade and oncogenic pathway activities, and two distinct microenvironmental patterns. The immune-activated CP(2)E microenvironment was composed of cancer-associated myofibroblasts, proinflammatory monocyte-derived macrophages, plasmacytoid dendritic cells and exhausted CD8+ T cells, and was prognostically unfavorable. In contrast, the inert N(3)MC microenvironment was characterized by normal-like myofibroblasts, non-inflammatory monocyte-derived macrophages, NK cells, myeloid dendritic cells and conventional T cells, and was associated with a favorable prognosis. Microenvironmental marker genes and signatures identified in single-cell profiles had progonostic value in bulk tumor profiles. In summary, single-cell RNA profiling of lung adenocarcinoma provides additional prognostic information based on the microenvironment, and may help to predict therapy response and to reveal possible target cell populations for future therapeutic approaches

The architecture of persistence : designing for future use

Buku ini membahas tentang arsitektur yang bertahan lama dan berkelanjutan, yang mampu beradaptasi dengan perubahan fisik dan budaya, serta menghubungkan masa lalu, sekarang, dan masa depan. Buku ini dilengkapi dengan puluhan wawancara dengan para arsitek dan pengguna bangunan, serta analisis ratusan proyek historis dan kontemporer. Buku ini menawarkan sejumlah prinsip dan contoh arsitektur yang bertahan lama dan berkelanjutan.viii, 303 p. : ill ; 27 cm

Assessing the \u27GEO\u27 in GEOCLUTTER: New Chirp Sonar, Sampling, and Compressional Wave Veolcity Results from the New Jersey Shelf

Geoclutter is a multi-year initiative supported by ONR to understand potential surficial and shallow sub-seafloor geologic causes for artifacts in tactical sonar returns. Following up a detailed acoustical characterization of a portion of the outer New Jersey continental shelf, two cruises have collected sediment samples, measured in-situ compressional wave velocities at the seafloor, and collected detailed 2D (200/400 m profile spacing) and pseudo-3D (50 m profile spacing) deep-towed chirp sonar profiles. In Area 1, ~20 (E-W) by ~26 km (N-S) in water depths 60-100 m, two distinct, shallowly buried, dendritic drainage systems trend generally NW-SE. Channels as small as 25 m wide and only 1-2 m deep can be resolved. Trunk channels are up to ~2 km wide and 12-15 m deep. Tributaries meander; N-S and SW-NE incisions are observed in both systems. Both of the drainage systems appear to outlet toward a broad gravel patch on the outer shelf, which was mapped by grab sampling and acoustic backscatter. Compressional velocities at the seafloor were measured by a probe recently developed at UNH. Observed values varied by sediment type. In Area 2, SW of Area 1, ~8 (E-W) by ~10 km (N-S), a less well-developed set of incisions appears to trend ~E-W. Some incisions in both areas correlate with ``clutter\u27\u27 targets previously mapped. To the north of Area 1, a series of E-W lines at 0.5 nmi spacing covers the outer shelf between the Hudson mid-shelf valley and the head of Hudson Canyon. A spectacular, buried, apparently meandering incision more than 1 nmi across may link the two seafloor features. Incision fill suggests early, rapid emplacement of debris/rubble(?), followed by more gradual(?) deposition of stratified material. We suspect that changes in filling style correlate with changes in the flow regime through the channel system through time, during the early part of the Holocene transgression. Total thickness of fill is 30 m or more. Relationships between drainage systems in Areas 1 and 2 and the larger ``proto-Hudson\u27\u27 channel system are not obvious, but must be complicated. Timing relationships among these features should be elucidated by drilling efforts planned for the New Jersey outer continental shelf in September 2002