Atlantic-origin water extension into the Pacific Arctic induced an anomalous biogeochemical event.

The Arctic Ocean is facing dramatic environmental and ecosystem changes. In this context, an international multiship survey project was undertaken in 2020 to obtain current baseline data. During the survey, unusually low dissolved oxygen and acidified water were found in a high-seas fishable area of the western (Pacific-side) Arctic Ocean. Herein, we show that the Beaufort Gyre shrinks to the east of an ocean ridge and forms a front between the water within the gyre and the water from the eastern (Atlantic-side) Arctic. That phenomenon triggers a frontal northward flow along the ocean ridge. This flow likely transports the low oxygen and acidified water toward the high-seas fishable area; similar biogeochemical properties had previously been observed only on the shelf-slope north of the East Siberian Sea.

Horizontal distribution of surface microplastic concentrations and water-column microplastic inventories in the Chukchi Sea, western Arctic Ocean.

The recent influx of microplastics into the Arctic Ocean may increase environmental stress on the western Arctic marine ecosystem, which is experiencing significant sea-ice loss due to global warming. Quantitative data on microplastics in the western Arctic Ocean are very limited, and the microplastic budget of the water column is completely unknown. To fill in gaps in our knowledge of Arctic microplastics, we observed surface concentrations (number of particles per unit volume of seawater) of meso- and microplastics using a neuston net, and we observed wind speeds and significant wave heights in the Chukchi Sea, Bering Strait, and Bering Sea. From these observations, we estimated the total number (particle inventory) and mass (mass inventory) of microplastics in the entire water column by taking into account the effect of vertical mixing. The particle inventory of microplastics in the Chukchi Sea ranged from 0 to 18,815 pieces km-2 with a mean and standard deviation of 5236 ± 6127 pieces km-2. The mass inventory ranged from 0 to 445 g km-2 with a mean and standard deviation of 124 ± 145 g km-2. Mean particle inventories for the Chukchi Sea were one-thirtieth of those for the Arctic Ocean on the Atlantic side and less than one-tenth of the average for the global ocean, suggesting that the Chukchi Sea is less polluted. However, the annual flux of microplastics from the Pacific Ocean into the Chukchi Sea, estimated from microplastic concentrations in the Bering Strait, was about 5.5 times greater than the total amount of microplastic in the entire Chukchi Sea water. This suggests that microplastic inflows from the Pacific Ocean are accumulating in large amounts in reservoirs other than the Chukchi Sea water (e.g., sea ice and seafloor sediments) or in the downstream regions of the Pacific-origin water.

Fukushima-derived radiocesium in the western subarctic area of the North Pacific Ocean, Bering Sea, and Arctic Ocean in 2019 and 2020.

We measured dissolved radiocesium (134Cs and 137Cs) in surface seawater collected in the western subarctic area of the North Pacific Ocean, Bering Sea, and Arctic Ocean in 2019 and 2020. The radiocesium released from the accident of the Fukushima Dai-ichi nuclear power plant (FNPP1) in 2011 was still observed in these areas (∼2 Bq m-3 decay-corrected to the date of the accident). In 2019/2020, the FNPP1-derived radiocesium concentrations in the Bering Sea and the Chukchi Sea, which is a marginal sea of the Arctic Ocean connecting the Bering Sea to the Arctic Ocean, were within the range of those observed in 2017/2018. On the other hand, the FNPP1-derived radiocesium was detected in the Arctic Ocean farther north of the Chukchi Sea in 2019/2020 for the first time. This was probably derived from the long-range transport of the FNPP1-derived radiocesium from the North Pacific coastal area of Japan to the Arctic Ocean through the Bering Sea during the past decade. The transport of the FNPP1-derived radiocesium from the Bering Sea to the western subarctic area in 2019/2020 is not clear, which implies the retainment of the FNPP1-derived radiocesium within the Bering Sea.

Zonal and vertical transports of Fukushima-derived radiocesium in the subarctic gyre of the North Pacific until 2014.

The Fukushima Dai-ichi Nuclear Power Plant (FNPP1) accident in March 2011 resulted in serious radiocesium contamination of the North Pacific Ocean. Most of the radiocesium was dissolved in seawater and transported by surface currents and subduction of mode waters. Within several years after the accident, a high-concentration water plume of the FNPP1-derived radiocesium at the sea surface had been transported from Japan to the North American continent across the subarctic gyre of the North Pacific Ocean. We measured vertical profiles of dissolved radiocesium along the nominal 47°N zonal line across the North Pacific subarctic gyre twice, in summer 2012 and summer 2014. Using these data and published data, we quantitatively discussed the zonal and vertical transports of the water plume until 2014. The FNPP1-derived radiocesium remained in the surface layer shallower than 200 m, which is the approximate winter mixed-layer depth in the western subarctic gyre. The mean penetration depth did not change between 2012 and 2014. The highest concentration was observed at 180°W in 2012 and at 151°W in 2014, which suggests that the zonal transport speed of the water plume in the eastern subarctic gyre was about 3.8 cm s-1. By combining the data from the zonal line in 2014 and a nominal 152°W meridional line in 2015, we elucidated the three-dimensional size of the high-concentration water plume in summer 2014. The total inventory of the FNPP1-derived radiocesium in the subarctic North Pacific Ocean, decay-corrected to the accident date, was estimated to be 12.0 ± 2.4 PBq.

Seasonal Water Mass Evolution and Non-Redfield Dynamics Enhance CO2 Uptake in the Chukchi Sea.

The Chukchi Sea is an increasing CO2 sink driven by rapid climate changes. Understanding the seasonal variation of air-sea CO2 exchange and the underlying mechanisms of biogeochemical dynamics is important for predicting impacts of climate change on and feedbacks by the ocean. Here, we present a unique data set of underway sea surface partial pressure of CO2 (pCO2) and discrete samples of biogeochemical properties collected in five consecutive cruises in 2014 and examine the seasonal variations in air-sea CO2 flux and net community production (NCP). We found that thermal and non-thermal effects have different impacts on sea surface pCO2 and thus the air-sea CO2 flux in different water masses. The Bering summer water combined with meltwater has a significantly greater atmospheric CO2 uptake potential than that of the Alaskan Coastal Water in the southern Chukchi Sea in summer, due to stronger biological CO2 removal and a weaker thermal effect. By analyzing the seasonal drawdown of dissolved inorganic carbon (DIC) and nutrients, we found that DIC-based NCP was higher than nitrate-based NCP by 66%-84% and attributable to partially decoupled C and N uptake because of a variable phytoplankton stoichiometry. A box model with a non-Redfield C:N uptake ratio can adequately reproduce observed pCO2 and DIC, which reveals that, during the intensive growing season (late spring to early summer), 30%-46% CO2 uptake in the Chukchi Sea was supported by a flexible stoichiometry of phytoplankton. These findings have important ramification for forecasting the responses of CO2 uptake of the Chukchi ecosystem to climate change.

[Two Cases in Which Simultaneous Laparoscopic Surgery and Breast Cancer Surgery Using a Head-Mounted Monitor Were Useful].

Herein, we report on how we were able to reduce the operation time by simultaneously performing laparoscopic surgery and breast cancer surgery using a head-mounted monitor(HMS-3000MT, Sony corporation). Case 1: 60s, female. A 5.5 cm leiomyoma was found in the central thoracic esophagus, and a 1 cm breast cancer was found in the C region of the left mammary gland. Subtotal esophagectomy with right thoracotomy and laparoscopy and a left partial mastectomy were performed. For the abdominal surgery, HMS-3000MT was used under hand-assisted laparoscopy, and a left partial mastectomy was performed concurrently. Operation time was 367 minutes(simultaneous surgery for 56 minutes). Esophagus: leiomyoma, 50×45 mm; and mammary gland: 16×15 mm, pTis(DCIS), pN0(sn), cM0, and pStage 0. Case 2: 70s, female. A 3 cm sized GIST was found on the posterior wall of the middle gastric body, and a breast cancer of 1.3 cm was also found in the B region of the right mammary gland. Using HMS-3000MT, laparoscopic local resection of the stomach and right total glandectomy were performed concurrently. Operation time was 114 minutes(simultaneous surgery for 58 minutes). Stomach: GIST, 25×22 mm, and modified Flecher classification low risk; and mammary gland: invasive ductal carcinoma, 15×15 mm, pT1c, pN0(sn), cM0, and pStage Ⅰ. Conclusion: In 2 fields of surgery, simultaneous surgery using HMS-3000MT was considered to be a useful method to shorten the operation time.

[A Case of Ectopic Pheochromocytoma between the Abdominal Aorta and Inferior Vena Cava].

We report a case of ectopic pheochromocytoma which is relatively rare. A 50-year-old man was found to have an abdominal tumor on a medical examination, and contrast-enhanced computed tomography showed a retroperitoneal tumor between the abdominal aorta and the inferior vena cava. As a result of close examinations, an ectopic pheochromocytoma was suspected. He was asymptomatic and suspected infiltrating into great vessels, but possibility of a malignant neoplasm could not be ruled out for the tumor had a tendency to enlarge, the resection of the tumor was performed. During the operation, the invasion of the tumor into the great vessels was denied and the tumor was completely resected. Large fluctuation of the blood pressure was not observed during the operation. Histopathological evaluations of the resected specimen revealed the ectopic pheochromocytoma. A pheochromocytoma was newly defined as a tumor with malignant potential for metastasis in all cases by the WHO classification published in 2017. He was diagnosed as moderately malignant by GAPP score, therefore the careful follow-up was considered necessary in the future.

[A Case of Metastatic Breast Cancer with BRCA1 Mutation after Breast Reconstruction and Pregnancy].

We present the case of a 31-year-old woman with a chief complaint of a left breast mass. The patient visited our department for an evaluation of this left breast mass. Left breast cancer(cT1cN0M0, cStage Ⅰ, triple negative type)was diagnosed, and left partial mastectomy and sentinel node biopsy were performed. Although the pStage was the same prior to surgery, a BRCA1 mutation was identified on genetic testing. After administration of postoperative adjuvant chemotherapy (epirubicin, cyclophosphamide, and paclitaxel), consorted mastectomy, tissue expander insertion, and breast reconstruction with silicone implant were performed. Spontaneous pregnancy occurred 1 year and 10 months after the first operation. She had an uneventful delivery with a normal course of labor 2 years and 6 months after the surgery. Two years and 11 months after the first operation, she visited our institution with complaints of headache, dizziness, and difficulty eating. Upon assessment, brain, lung, liver, and bone metastases were identified on contrast-enhanced computed tomography. Concentrated glycerin and fructose, steroid administration, and whole-brain irradiation improved the symptoms due to cerebral edema. Thereafter, olaparib was started, and treatment was continued while maintaining partial response(PR).

Multiple developmental pathways lead to the generation of CD4 T-cell memory.

Long-term immunological memory mediated by CD4 T cells provides a rapid protection against previously encountered pathogens or antigens. However, it is still controversial how memory CD4 T cells are generated and maintained. Unclear definitions of T-cell memory may be partially responsible for this controversy. It is becoming clear that diverse pathways are responsible for the differentiation and long-term persistence of memory T cells. We herein discuss the diversity of memory cell generation, describing a novel population of resting memory CD4 T cells and their precursors.

Overexpression of miR-669m inhibits erythroblast differentiation.

MicroRNAs (miRNAs), one of small non-coding RNAs, regulate many cell functions through their post-transcriptionally downregulation of target genes. Accumulated studies have revealed that miRNAs are involved in hematopoiesis. In the present study, we investigated effects of miR-669m overexpression on hematopoiesis in mouse in vivo, and found that erythroid differentiation was inhibited by the overexpression. Our bioinformatic analyses showed that candidate targets of miR-669m which are involved in the erythropoiesis inhibition are A-kinase anchoring protein 7 (Akap7) and X-linked Kx blood group (Xk) genes. These two genes were predicted as targets of miR-669m by two different in silico methods and were upregulated in late erythroblasts in a public RNA-seq data, which was confirmed with qPCR. Further, miR-669m suppressed luciferase reporters for 3' untranslated regions of Akap7 and Xk genes, which supports these genes are direct targets of miR-669m. Physiologically, miR-669m was not expressed in the erythroblast. In conclusion, using miR-669m, we found Akap7 and Xk, which may be involved in erythroid differentiation, implying that manipulating these genes could be a therapeutic way for diseases associated with erythropoiesis dysfunction.

Local injection of CCL19-expressing mesenchymal stem cells augments the therapeutic efficacy of anti-PD-L1 antibody by promoting infiltration of immune cells.

BACKGROUND: Mesenchymal stem/stromal cells (MSC) accumulate and reside in tumor sites. METHODS: Taking advantage of this feature in anticancer therapy, immortalized murine MSC (iMSC) were genetically altered to produce chemokine (C-C motif) ligand 19 (iMSC/CCL19), which attracts dendritic cells (DC) and T lymphocytes. Thereafter, iMSC/CCL19 were examined for their therapeutic efficacy using a syngeneic CT26 colon carcinoma cell line. RESULTS: Co-injection of iMSC/CCL19 into mice significantly suppressed the in vivo growth of CT26 cells compared with that of CCL19-expressing immortalized fibroblasts (iFib/CCL19). This anticancer effect was not observed when injected in CT26-bearing nude mice. Co-injected iMSC/CCL19 survived longer than iFib/CCL19 in the tumor sites. In a therapeutic model, local injection of iMSC/CCL19 suppressed the tumor growth, and increased IFN (interferon)-γ+ CD8+ T cells and CCR7+ DC infiltration in tumor site was observed when treated with iMSC/CCL19, but not with iMSC. This antitumor effect was completely negated by depletion of CD4+ cells and partially negated by depletion of CD8+ cells. Furthermore, the antitumor effects induced by local injection of iMSC/CCL19 were augmented by additional therapy with anti-programmed death (PD)-ligand 1 (PD-L1) antibody, but not with anti-PD-1 antibody. This combination therapy cured most of the tumors in CT26-bearing mice. CONCLUSION: These results suggest that local therapy with iMSC/CCL19 can suppress tumor growth via effective recruitment of CCR7+ DC into tumor sites and increase IFN-γ+ CD8+ T cells, and that combination with anti-PD-L1 antibody therapy can be a powerful anticancer therapy.

CD4+ Resident Memory T Cells Mediate Long-Term Local Skin Immune Memory of Contact Hypersensitivity in BALB/c Mice.

In allergic contact dermatitis (ACD) and contact hypersensitivity (CHS), the healed skin shows greater swelling than the naïve skin in the same individual upon re-exposure to the same hapten. This "local skin memory" (LSM) in healed skin was maintained for a prolonged period of time and mediated by skin CD8+-resident memory T (TRM) cells in C57BL/6 mice. However, the number of CD4+ T cells is elevated in ACD-healed human skin, and the contribution of CD4+ TRM cells to the formation of LSM currently remains unclear. We herein demonstrated that immediately after CHS subsided, the healed skin in BALB/c mice showed an accumulation of hapten-specific CD4+ and CD8+ TRM cells, with a predominance of CD4+ TRM cells. The presence of CD4+ or CD8+ TRM cells in the healed skin was sufficient for the induction of a flare-up reaction upon a re-challenge. The CD4+ and CD8+ TRM cells both produced interferon-γ and tumor necrosis factor early after the re-challenge. Moreover, while CD8+ TRM cells gradually decreased over time and were eventually lost from the healed skin at 40-51 weeks after the resolution of CHS, the CD4+ TRM cell numbers remained elevated during this period. The present results indicate that the long-term maintenance of LSM is mediated by CD4+ TRM cells, and thus CD4+ TRM cells are an important target for the treatment of recurrent human ACD.

Global Ocean Spectrophotometric pH Assessment: Consistent Inconsistencies.

Ocean acidification (OA)-or the decrease in seawater pH resulting from ocean uptake of CO2 released by human activities-stresses ocean ecosystems and is recognized as a Climate and Sustainable Development Goal Indicator that needs to be evaluated and monitored. Monitoring OA-related pH changes requires a high level of precision and accuracy. The two most common ways to quantify seawater pH are to measure it spectrophotometrically or to calculate it from total alkalinity (TA) and dissolved inorganic carbon (DIC). However, despite decades of research, small but important inconsistencies remain between measured and calculated pH. To date, this issue has been circumvented by examining changes only in consistently measured properties. Currently, the oceanographic community is defining new observational strategies for OA and other key aspects of the ocean carbon cycle based on novel sensors and technologies that rely on validation against data records and/or synthesis products. Comparison of measured spectrophotometric pH to calculated pH from TA and DIC measured during the 2000s and 2010s eras reveals that (1) there is an evolution toward a better agreement between measured and calculated pH over time from 0.02 pH units in the 2000s to 0.01 pH units in the 2010s at pH > 7.6; (2) a disagreement greater than 0.01 pH units persists in waters with pH < 7.6, and (3) inconsistencies likely stem from variations in the spectrophotometric pH standard operating procedure (SOP). A reassessment of pH measurement and calculation SOPs and metrology is urgently needed.

Determining the Distribution of Fluorescent Organic Matter in the Indian Ocean Using in situ Fluorometry.

In order to determine the dynamics of marine fluorescent organic matter (FOM) using high-resolution spatial data, in situ fluorometers have been used in the open ocean. In this study, we measured FOM during the Global Ocean Ship-based Hydrographic Investigations Program (GO-SHIP) expedition from early December 2019 to early February 2020, using an in situ fluorometer at 148 stations along the two meridional transects (at ∼80 and ∼57°E) in the Indian Ocean, covering latitudinal ranges from ∼6°N to ∼20°S and ∼30 to ∼65°S, respectively. The FOM data obtained from the fluorometer were corrected for known temperature dependence and calibrated using FOM data measured onboard by a benchtop fluorometer. Using the relative water mass proportions estimated from water mass analyses, we determined the intrinsic values of FOM and apparent oxygen utilization (AOU) for each of the 12 water masses observed. We then estimated the basin-scale relationship between the intrinsic FOM and the AOU, as well as the turnover time for FOM in the Indian Ocean (410 ± 19 years) in combination with the microbial respiration rate in the dark ocean (>200 m). Consistent to previous estimates in the global tropical and subtropical ocean, the FOM turnover time obtained is of the same order of magnitude as the circulation age of the Indian Ocean, indicating that the FOM is refractory and is a sink for reduced carbon in the dark ocean. A decoupling of FOM and AOU from the basin-scale relationship was also observed in the abyssal waters of the northern Indian Ocean. The local variability may be explained by the effect of sinking organic matter altered by denitrification through the oxygen-deficient zone on enhanced abyssal FOM production relative to oxygen consumption.

[A Case of Laparoscopic Distal Gastrectomy for Gastric Cancer with an Adachi Type â ¥ Group 24 Vascular Anomaly].

We report a case of successful laparoscopic distal gastrectomy for gastric cancer with an Adachi type Ⅵ group 24 vascular anomaly. A male in his 60s exhibited a type 0-Ⅱa plus Ⅱc lesion at the lesser curvature of the gastric angle by esophagogastroduodenoscopy and was diagnosed with tub2. He was referred to us for surgical treatment. The clinical diagnosis was cT1bN0M0, and cStage Ⅰ. Preoperative multidetector-row computed tomography(MDCT)showed an Adachi type Ⅵ group 24 vascular anomaly. At laparoscopic surgery, we dissected No. 8a lymph nodes with exposure of the surface of the portal vein because the common hepatic artery was absent. The left gastric artery and splenic artery formed a common trunk. As there are various kinds of vascular anomalies of the celiac artery branch, we must understand the arterial running pattern prior to gastric surgery. This technique is more useful in laparoscopic surgeries where tactile sensation is limited. To prevent perioperative and postoperative complications, we must recognize the anomaly pattern prior to surgery using MDCT.

Decadal acidification in Atlantic and Mediterranean water masses exchanging at the Strait of Gibraltar.

Seawater pH is undergoing a decreasing trend due to the absorption of atmospheric CO2, a phenomenon known as ocean acidification (OA). Biogeochemical processes occurring naturally in the ocean also change pH and hence, for an accurate assessment of OA, the contribution of the natural component to the total pH variation must be quantified. In this work, we used 11 years (2005-2015) of biogeochemical measurements collected at the Strait of Gibraltar to estimate decadal trends of pH in two major Mediterranean water masses, the Western Mediterranean Deep Water (WMDW) and the Levantine Intermediate Water (LIW) and assess the magnitude of natural and anthropogenic components on the total pH change. The assessment was also performed in the North Atlantic Central Water (NACW) feeding the Mediterranean Sea. Our analysis revealed a significant human impact on all water masses in terms of accumulation of anthropogenic CO2. However, the decadal pH decline found in the WMDW and the NACW was markedly affected by natural processes, which accounted for by nearly 60% and 40% of the total pH decrease, respectively. The LIW did not exhibit a significant pH temporal trend although data indicated natural and anthropogenic perturbations on its biogeochemical signatures.

The oceanic sink for anthropogenic CO2 from 1994 to 2007.

We quantify the oceanic sink for anthropogenic carbon dioxide (CO2) over the period 1994 to 2007 by using observations from the global repeat hydrography program and contrasting them to observations from the 1990s. Using a linear regression-based method, we find a global increase in the anthropogenic CO2 inventory of 34 ± 4 petagrams of carbon (Pg C) between 1994 and 2007. This is equivalent to an average uptake rate of 2.6 ± 0.3 Pg C year-1 and represents 31 ± 4% of the global anthropogenic CO2 emissions over this period. Although this global ocean sink estimate is consistent with the expectation of the ocean uptake having increased in proportion to the rise in atmospheric CO2, substantial regional differences in storage rate are found, likely owing to climate variability-driven changes in ocean circulation.

[A Case in Which Trastuzumab Combined Chemotherapy Was Effective for Recurrence of Post-Operative Gastric Cancer with Partial HER2 Overexpression].

We report a case in which recurrent partial HER2-positive gastric cancer showed complete clinical response to capecitabine (Cape)/oxaliplatin(L-OHP/OX)(CapeOX)plus trastuzumab(Tmab)combined chemotherapy for 32months. A 65-yearold man underwent distal gastrectomy, D2 lymph node dissection, and Roux-en-Y reconstruction for type 2 gastric cancer of the prepyloric anterior wall in December 2014. Pathological stage was as follows: L, ant, Type 2, 32×22 mm, tub1>tub2> por1, pT2(MP), int>med, INF c>a, Ly1a, V0, pN0, cM0, cH0, cP0, pCY0, pStage I B, pPM0(60mm), pDM0(75mm), pR0. Immunostaining of the tumor indicated overexpression of the HER2 gene in more than 10% of the well differentiated tubular adenocarcinoma(tub1). Nineteen months post-surgery, pancreatic head lymph node metastasis was diagnosed, and we started CapeOX plus Tmab combined chemotherapy. After 19 courses, the metastatic lymph node reduced its size until we could not detect it on CT. We continued treatment for 45 courses(about 32 months). During the courses, there were adverse events such as peripheral neuropathy(Grade 3, CTCAE v5.0), which required interruption of L-OHP, and oral mucosal ulcer (Grade 2).

Effect of lateral lymph node dissection for mid and low rectal cancer: An ad-hoc analysis of the ACTS-RC (JFMC35-C1) randomized clinical trial.

BACKGROUND: Lateral lymph node dissection has been 1 of the standard treatments for mid and ow rectal cancer in Japan. The aim of this ad-hoc analysis was to evaluate the impact of lateral lymph node dissection on outcomes in the randomized clinical trial, referred to as the Adjuvant Chemotherapy for Stage II/III Rectal Cancer trial. METHODS: The Adjuvant Chemotherapy for Stage II/III Rectal Cancer trial was a randomized, phase III trial of adjuvant chemotherapy of 2 different oral fluoropyrimidines; 445 patients with lower rectal cancer were studied in this ad-hoc analysis out of 959 patients in total, 215 of whom underwent lateral lymph node dissection and 230 did not. RESULTS: There were no significant differences in background characteristics of the patients in the group, except for in age and number of dissected lymph nodes, between the lateral lymph node dissection and without lateral lymph node dissection groups. The age of the younger patients was often used to select candidates for lateral lymph node dissection (lateral lymph node dissection versus non-lateral lymph node dissection; 63.5 ± 8.9 vs 60.7 ± 9.4 [P = .0017]). Lateral lymph node dissection had no impact on relapse-free survival (hazard ratio = 0.941, 95% confidence interval: 0.696-1.271) or overall survival (hazard ratio = 0.858, 95% confidence interval: 0.601-1.224) in all patients with mid and low rectal cancer. In subset analysis, lateral lymph node dissection improved relapse-free survival in female patients and in patients with stage B/C or N3/4 disease. For cumulative recurrence across all patients, the proportion of patients with distant recurrence was slightly greater in the lateral lymph node dissection group but there was no difference in local recurrence. CONCLUSION: This exploratory analysis did not show that lateral lymph node dissection improves relapse-free survival and overall survival in patients with mid and low rectal cancer. Lateral lymph node dissection may, however, have a prognostic impact on patients with highly invasive rectal cancer.

Kit-independent mast cell adhesion mediated by Notch.

Kit/CD117 plays a crucial role in the cell-cell and cell-matrix adhesion of mammalian mast cells (MCs); however, it is unclear whether other adhesion molecule(s) perform important roles in the adhesion of MCs. In the present study, we show a novel Kit-independent adhesion mechanism of mouse cultured MCs mediated by Notch family members. On stromal cells transduced with each Notch ligand gene, Kit and its signaling become dispensable for the entire adhesion process of MCs from tethering to spreading. The Notch-mediated spreading of adherent MCs involves the activation of signaling via phosphatidylinositol 3-kinases and mitogen-activated protein kinases, similar to Kit-mediated spreading. Despite the activation of the same signaling pathways, while Kit supports the adhesion and survival of MCs, Notch only supports adhesion. Thus, Notch family members are specialized adhesion molecules for MCs that effectively replace the adhesion function of Kit in order to support the interaction of MCs with the surrounding cellular microenvironments.