Real-world outcomes of third-line immune checkpoint inhibitors versus irinotecan-based chemotherapy in patients with advanced gastric cancer: a Korean, multicenter study (KCSG ST22-06).

BACKGROUND: Immune checkpoint inhibitor (ICI) or irinotecan-based chemotherapy is frequently used after failure of second-line paclitaxel plus ramucirumab treatment for patients with locally advanced unresectable or metastatic advanced gastric cancer (AGC). This study aimed to compare the efficacy between ICI and irinotecan-based chemotherapy as third-line treatment in patients with AGC. METHODS: We retrospectively reviewed patients with AGC, whose third-line treatment started between July 2019 and June 2021 at 17 institutions in Korea. The ICI group included patients who received nivolumab or pembrolizumab, and the irinotecan-based chemotherapy group included patients who received irinotecan or FOLFIRI (5-fluorouracil, leucovorin and irinotecan). RESULTS: A total of 363 patients [n = 129 (ICI) and n = 234 (irinotecan-based chemotherapy)] were analyzed. The median progression-free survival was 2.3 and 2.9 months in ICI and irinotecan-based chemotherapy groups, respectively (p = 0.802). The median overall survival (OS) was 5.5 and 6.0 months in ICI and irinotecan-based chemotherapy groups, respectively (p = 0.786). For all patients included in this study, multivariable analysis showed that weight loss, peritoneal metastasis, low serum sodium or albumin, and short duration of second-line treatment were associated with inferior OS (p < 0.05). ICI showed significantly longer OS than irinotecan-based chemotherapy in patients without peritoneal metastasis. Whereas ICI showed significantly shorter OS in patients without PD-L1 expression than irinotecan-based chemotherapy. CONCLUSIONS: No significant difference in survival outcome was observed between ICI and irinotecan-based chemotherapy as third-line treatment for AGC patients. ICI might be preferred for patients without peritoneal metastasis and irinotecan-based chemotherapy for patients with tumors without PD-L1 expression. TRIAL REGISTRATION: This study was registered in the Clinical Trial Registry of Korea ( https://cris.nih.go.kr : KCT 0007732).

A simple method for extracting phycocyanin from Arthrospira (Spirulina) platensis by autolysis.

Phycocyanin (PC) is a natural blue pigment that has great commercial value in food and pharmaceutical industry. Arthrospira (Spirulina) platensis is a photosynthetic spiral-shaped cyanobacterium containing a rich PC pigment. Autolysis is the enzymatic digestion of cells by the action of its own enzymes. To develop an effective and economical extraction process, an autolysis process was incorporated into the conventional freezing-thawing method. In the present study, 91% of maximal extraction yield of PC with 1.194 purity (A620/A280) was obtained via autolysis after 3 h of incubation at 37 °C without using an extraction salt solution or a successive freezing-thawing process. In addition to temperature, the initial concentration of bicarbonate in growth medium and the concentration of wet biomass are important parameters that influence the extraction yield of PC by autolysis.

Treatment and Outcomes of Metastatic Pancreatic Cancer in Elderly Patients.

BACKGROUND AND AIMS: Although pancreatic cancers are common in older age-groups, the prognosis remains poor due to limited studies on treatment approaches and outcomes in a given population. We aimed to examine treatment patterns and their outcomes in older patients with metastatic pancreatic cancer in a real-world context. MATERIALS AND METHODS: We conducted a retrospective study including 167 patients with metastatic pancreatic cancer (aged ≥70 years and male/female: 78/89) between January 2010 and July 2015. Patients' retrieved data from medical records were analyzed according to treatment types, followed by a review of clinicopathologic variables and treatment outcomes. RESULTS: Of the 167 eligible patients for the study, only 21.6% (n = 36) received palliative chemotherapy. The median age of the chemotherapy group was 74.0 years and 78.6 years for the supportive care group. The median survival of the chemotherapy group was 9.2 months (range: 1.0-24.9 months), compared with that of the supportive care group, which was 2.3 months (range: 0.1-31.8 months). Among the patients in the chemotherapy group, 50% (n = 18) received gemcitabine-based double therapy, and 30% patients (n = 9) received second-line chemotherapy. CONCLUSIONS: Our results showed that older patients with metastatic pancreatic cancer were less likely to receive chemotherapy. However, the survival benefit from chemotherapy was comparable to that of younger patients' counterpart. Thus, further study involving identification of older patients who would benefit from cytotoxic chemotherapy is needed.

Tuna byproducts as a fish-meal in tilapia aquaculture.

Potentiality of the use of tuna byproducts as a fish-meal replacement on Nile tilapia (Oreochromis niloticus) was examined for 84 weeks by tracking the concentrations of cadmium and mercury in the internal organs, muscles and fish whole body through generation including their immature eggs and their larvae. The results confirmed that the tuna byproducts can be used as a fish-meal substitute in tilapia aquaculture, because their acceptable ranges for cadmium and mercury consequently did not exceed the food safety values (both < 0.5 mg kg-1), despite their proportional increases in the fish body. The use of tuna byproducts as a protein source is expected to reduce the cost of feed with other fishmeal substitutes in tilapia aquaculture. However, fish (flounder) indiscriminately consuming tuna byproduct feed were prohibited and recalls of sales were issued by the government (July 2018, Republic of Korea), as the threshold for mercury in the fish bodies had been exceeded (0.6-0.8 mg kg-1). Further study of the use of tuna byproducts as fishmeal replacements for other species in aquaculture is needed, as concentration ratios can vary depending on the species.

Size-dependent hardness of five-fold twin structured Ag nanowires.

In this study, the size dependent hardness of silver nanowires with a five-fold twin structure was examined using nanoindentation. As the diameter of the nanowires is reduced, the five-fold twin boundaries restrict the dislocation motion, and therefore a size dependent plasticity is expected for these uniquely structured nanowires. The polyol reduction method with modifications was used to synthesize silver nanowires with different diameters in the range of 70 nm to 144 nm. The nanoindentation experiments were performed on silver nanowires deposited on a stiff MgO substrate, and the resulting h, P, and S data were analyzed using the analytical double contact model for nanowire indentation. The hardness of the nanowires determined using the double contact model showed an increase in the hardness with reduction in the diameter of the nanowires, as expected due to the presence of the twin boundaries. The hardness values determined using the analytical double contact model compared favorably to the hardness values calculated from the contact areas that were extracted from finite element method simulations of an elastic indentation into the silver nanowires on the MgO substrate.

Phase II study of docetaxel, oxaliplatin, and S-1 therapy in patients with metastatic gastric cancer.

BACKGROUND: Although the docetaxel, 5-fluorouracil, and cisplatin triplet has yielded significant improvements in time to progression, overall survival, and overall response rate, the high incidence of severe adverse events limits the use of the docetaxel, 5-fluorouracil, and cisplatin triplet. To overcome this limitation, we evaluated the efficacy and safety of the combination of docetaxel, oxaliplatin, and S-1 for the treatment of metastatic gastric cancer. METHODS: Chemotherapy-naive patients with pathologically proven unresectable recurrent or metastatic gastric adenocarcinoma were assessed for eligibility. Docetaxel at 52.5 mg/m(2) and oxaliplatin at 105 mg/m(2) were administered intravenously on day 1, and S-1 was administered orally at 80 mg/m(2) on days 1-14 of every 21-day cycle. RESULTS: Forty-four patients (median age 54.5 years) were enrolled. All patients had metastatic disease. A total of 340 cycles of chemotherapy were administered (median of eight cycles per patient; range 1-36 cycles). Toxicities were evaluated in 43 patients, and the responses were evaluated in 40 patients. Major toxicities included grade 3/4 neutropenia (37.2 %) and leukopenia (27.9 %). The overall response rate was 54.5 % [95 % confidence interval (CI) 40.1-68.3 %] in the intention-to-treat population. The median progression-free survival and overall survival were 7.6 months (95 % CI 6.2-9.0 months) and 12.0 months (95 % CI 6.9-17.2 months), respectively. CONCLUSION: These data suggest that the docetaxel, oxaliplatin, and S-1 combination regimen is effective and relatively well tolerable, and it seems to have potential to be a reasonable therapeutic strategy in patients with metastatic or recurrent gastric cancer.

Trusting Social Media as a Source of Health Information: Online Surveys Comparing the United States, Korea, and Hong Kong.

BACKGROUND: The Internet has increasingly become a popular source of health information by connecting individuals with health content, experts, and support. More and more, individuals turn to social media and Internet sites to share health information and experiences. Although online health information seeking occurs worldwide, limited empirical studies exist examining cross-cultural differences in perceptions about user-generated, experience-based information compared to expertise-based information sources. OBJECTIVE: To investigate if cultural variations exist in patterns of online health information seeking, specifically in perceptions of online health information sources. It was hypothesized that Koreans and Hongkongers, compared to Americans, would be more likely to trust and use experience-based knowledge shared in social Internet sites, such as social media and online support groups. Conversely, Americans, compared to Koreans and Hongkongers, would value expertise-based knowledge prepared and approved by doctors or professional health providers more. METHODS: Survey questionnaires were developed in English first and then translated into Korean and Chinese. The back-translation method ensured the standardization of questions. Surveys were administered using a standardized recruitment strategy and data collection methods. RESULTS: A total of 826 participants living in metropolitan areas from the United States (n=301), Korea (n=179), and Hong Kong (n=337) participated in the study. We found significant cultural differences in information processing preferences for online health information. A planned contrast test revealed that Koreans and Hongkongers showed more trust in experience-based health information sources (blogs: t451.50=11.21, P<.001; online support group: t455.71=9.30, P<.001; social networking sites [SNS]: t466.75=11.36, P<.001) and also reported using blogs (t515.31=6.67, P<.001) and SNS (t529.22=4.51, P<.001) more frequently than Americans. Americans showed a stronger preference for using expertise-based information sources (eg, WebMD and CDC) compared to Koreans and Hongkongers (t360.02=3.01, P=.003). Trust in expertise-based information sources was universal, demonstrating no cultural differences (Brown-Forsythe F2,654=1.82, P=.16). Culture also contributed significantly to differences in searching information on behalf of family members (t480.38=5.99, P<.001) as well as to the goals of information searching. CONCLUSIONS: This research found significant cultural differences in information processing preferences for online health information. Further discussion is included regarding effective communication strategies in providing quality health information.

Utilization of seawater for cost-effective cultivation and harvesting of Scenedesmus obliquus.

Microalgae hold great promise as a source of biofuels and biochemicals. The main obstacles to their industrial application are the high cultivation and downstream costs related to media and harvesting. In the work, we explored the multiple potentials of seawater to address key issues relating to the cultivation of Scenedesmus obliquus. Seawater can sufficiently replace some of the key elements in BG11 medium such as MgSO4, CaCl2, and NaCO3, and its use can significantly reduce the quantity of water required for the preparation of culture media. Among our results, the total chlorophyll content in cells grown in modified BG11 using 10 % (v/v) seawater was increased 1.47-fold without sacrificing biomass or lipid production. More than 70 % of the total algal biomass was auto-flocculated within one hour when cells were grown in seawater-supplemented media, which compares very favorably with a yield of only 3 % from cells grown in BG11.

Optimization of variables affecting the direct transesterification of wet biomass from Nannochloropsis oceanica using ionic liquid as a co-solvent.

Ionic liquids have many applications, one of which entails their utilization as powerful solvents. In the present study, various experimental conditions of ionic liquid-mediated direct transesterification were investigated in terms of lipid-extracting ionic liquids, catalyst, reaction time, reaction temperature and volume of methanol to achieve effective FAME conversion with wet microalgal feedstock, Nannochloropsis oceanica. With ionic liquid, [Bmim][CF3SO3], highest fatty acid methyl ester (FAME) yield was shown. Among many experimental parameters, the two most critical factors to enhance FAME conversion were characteristic of ionic liquids and volume of methanol. Optimized ionic liquid-mediated direct transesterification of wet N. oceanica, compared with a control experiment using chloroform and methanol, increased the FAME conversion yield by 11-fold.

Multi-level functionality of social media in the aftermath of the Great East Japan Earthquake.

This study examines the multi-level functionalities of social media in the aftermath of the Great East Japan Earthquake of 11 March 2011. Based on a conceptual model of multi-level story flows of social media (Jung and Moro, 2012), the study analyses the multiple functionalities that were ascribed to social media by individuals, organisations, and macro-level social systems (government and the mass media) after the earthquake. Based on survey data, a review of Twitter timelines and secondary sources, the authors derive five functionalities of social media: interpersonal communications with others (micro level); channels for local governments; organisations and local media (meso level); channels for mass media (macro level); information sharing and gathering (cross level); and direct channels between micro-/meso- and macro-level agents. The study sheds light on the future potential of social media in disaster situations and suggests how to design an effective communication network to prepare for emergency situations.

Effects of molten-salt/ionic-liquid mixture on extraction of docosahexaenoic acid (DHA)-rich lipids from Aurantiochytrium sp. KRS101.

In this study, lipid extraction from Aurantiochytrium sp. was performed using a molten-salt/ionic-liquid mixture. The total fatty acid content of Aurantiochytrium sp. was 478.8 mg/g cell, from which 145 mg/g cell (30.3% of total fatty acids) of docosahexaenoic acid (DHA) was obtained. FeCl3·6H2O showed a high lipid extraction yield (207.9 mg/g cell), when compared with that of [Emim]OAc, which was only 118.1 mg/g cell; notably however, when FeCl3·6H2O was mixed with [Emim]OAc (5:1, w/w), the yield was increased to 478.6 mg/g cell. When lipid was extracted by the FeCl3·6H2O/[Emim]OAc mixture at a 5:1 (w/w) blending ratio under 90 °C, 30 min reaction conditions, the fatty acid content of the extracted lipid was a high purity 997.7 mg/g lipid, with most of the DHA having been extracted (30.2% of total fatty acids). Overall, lipid extraction from Aurantiochytrium sp. was enhanced by the synergistic effects of the molten-salt/ionic-liquid mixture with different ions.

Use of extracts from oyster shell and soil for cultivation of Spirulina maxima.

Calcium ion and trace metals play important roles in various metabolisms of photosynthetic organisms. In this study, simple methods were developed to extract calcium ion and micronutrients from oyster shell and common soil, and the prepared extracts were tested as a replacement of the corresponding chemicals that are essential for growth of microalgae. The oyster shell and soil were treated with 0.1 M sodium hydroxide or with 10 % hydrogen peroxide, respectively. The potential application of these natural sources to cultivation was investigated with Spirulina maxima. When compared to standard Zarrouk medium, the Spirulina maxima cultivated in a modified Zarrouk media with elements from oyster shell and soil extract exhibited increases in biomass, chlorophyll, and phycocyanin by 17, 16, and 64 %, respectively. These results indicate that the extracts of oyster shell and soil provide sufficient amounts of calcium and trace metals for successful cultivation of Spirulina maxima.

Limitations and high pressure behavior of MOF-5 for CO2 capture.

Porous network structures (e.g. metal-organic frameworks, MOFs) show considerable potential in dethroning monoethanol amine (MEA) from being the dominant scrubber for CO2 at the fossil-fuel-burning power generators. In contrast to their promise, structural stability and high-pressure behavior of MOFs are not well documented. We herein report moisture stability, mechanical properties and high-pressure compression on a model MOF structure, MOF-5. Our results show that MOF-5 can endure all tested pressures (0-225 bar) without losing its structural integrity, however, its moist air stability points at a 3.5 hour safety window (at 21.6 °C and 49% humidity) for an efficient CO2 capture. Isosteric heats of CO2 adsorption at high pressures show moderate interaction energy between CO2 molecules and the MOF-5 sorbent, which combined with the large sorption ability of MOF-5 in the studied pressure-temperature ranges show the viability of this sorbent for CO2 capturing purposes. The combination of the physicochemical methods we used suggests a generalized analytical standard for measuring viability in CO2 capture operations.

Predictors of high score patient-reported barriers to controlling cancer pain: a preliminary report.

PURPOSE: Pain is one of the most common and devastating symptoms in cancer patients, and misunderstandings on the patient's part can cause major obstacles in pain management. METHOD: We evaluated factors associated with patient's high barrier score to managing cancer-associated pain by having 201 patients complete the Korean Barriers Questionnaire II, the Brief Pain Inventory--Korean, the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30, and the Korean Beck Depression Inventory. The Pain Management Index (PMI) was also assessed. RESULTS: The patients were from nine oncology clinics in university hospitals and a veterans' hospital in South Korea. The median pain score (0-10 scale) was 4, with a median percentage of pain improvement during the last 24 h of 70 %. A total of 150 patients (75 %) received strong opioids, and 177 (88 %) achieved adequate analgesia (positive PMI). Mean scores ± SD for the Barriers Questionnaire II ranged from 1.5 ± 1 to 2.8 ± 1.1, with the harmful effects subscale the highest. In the multiple regression model, depression was significantly associated with total barrier score to pain management (p < 0.0001). Pain reduction was significantly associated with the fatalism subscale. CONCLUSIONS: Depression was associated with high barrier score in patients with cancer pain. Management of cancer pain should include screening for depression, and management of depression could reduce patient-reported barriers to pain management.

Photometric determination of peracetic acid by reaction with potassium iodide solution.

Peracetic acid (PAA) is a strong oxidizing agent and is considered an ideal disinfectant because of its excellent disinfecting effect at low concentration, low corrosiveness, and relatively low cost. Commercially available PAA solution is a mixture of PAA, acetic acid, and hydrogen peroxide. However, PAA naturally decomposes faster than hydrogen peroxide. Therefore, accurately quantifying the concentration of PAA in the PAA peroxide mixture via a simple method is important. In the present study, a new method was developed, in which the spectral change of I- ion at 226 nm and the absorption value from the generated I2 at 460 nm were used to determine the concentration of PAA, following a chemical reaction with 0.1 mM potassium iodide (KI) solution without the use of any other chemicals. In this work, the measurable concentration of PAA was as low as 0.0001 wt% (13.1 µM) and as high as 0.0015 wt% (197.2 µM), which matches well with high linearity (99.95% at 226 nm and 99.91% at 460 nm). This work could also be the high selectivity method toward PAA in the PAA peroxide mixture.

A simple spectrophotometric determination of hydrogen peroxide solution via spectral delta from redox reaction with sodium hypochlorite.

Hydrogen peroxide (H2O2) is widely used in the synthesis of organic chemicals, bleaching of paper pulp, and the treatment of wastewater and as a food additive, important mediator of redox processes in natural water, and a disinfectant. However, H2O2 stock solution is unstable and slowly decomposes when exposed to, for example, light, elevated temperatures, or metal compounds. Therefore, the ability to measure the exact concentration of H2O2 stock solution is important for its proper use in diverse applications. This work proposes a simple method for the spectrophotometric determination of H2O2 solution via chemical reaction with sodium hypochlorite that is inexpensive and easy to acquire. The proposed method is based on the stoichiometric spectral change of hypochlorite ion at 292.5 nm following a redox reaction with a sample solution of H2O2. Due to high relationship between the spectral delta value and the applied H2O2 concentration (0.00188-0.03000%), H2O2 stock solution can be easily quantified.

Less-Suture Vascular Anastomosis: Development of Alternative Protocols with Multifunctional Self-Wrapping, Transparent, Adhesive, and Elastic Biomaterials.

Blood vessel anastomosis by suture is a life-saving, yet time-consuming and labor-intensive operation. While suture-less alternatives utilizing clips or related devices are developed to address these shortcomings, suture anastomosis is still overwhelmingly used in most cases. In this study, practical "less-suture" strategies are proposed, rather than ideal "suture-less" methods, to reflect real-world clinical situations. In the case of rat artery (d = 0.64 mm) anastomosis, the less-suture anastomosis involves the application of thin, adhesive, transparent, and self-wrapping films to the site. This surprisingly reduces the number of stitches required from ten (without films) to four (with films), saving 27 min of operating time per vessel. Furthermore, the decreased number of stitches largely alleviates fibrosis-mediated wall-thickening. Thus, a less-suture strategy is particularly useful for anastomosis of multiple vessels in emergency conditions and small-diameter vessels.

A phase II study of chemotherapy in combination with telomerase peptide vaccine (GV1001) as second-line treatment in patients with metastatic colorectal cancer.

Background: GV1001 is a human telomerase peptide vaccine that induces a CD4/CD8 T-cell response against cancer cells, thereby affording an immunological anti-tumor effect. Here, we evaluated the efficacy and safety of GV1001 in combination with chemotherapy in patients with metastatic colorectal cancer who had failed first-line chemotherapy. Methods: This multicenter, non-randomized, single-arm phase II study recruited recurrent or metastatic colorectal cancer patients with measurable disease who had failed first-line chemotherapy. Patients received GV1001 and chemotherapy concomitantly based on a pre-established schedule. Cytotoxic chemotherapy and targeted agents (bevacizumab, cetuximab, or aflibercept) were allowed to be used at the discretion of the investigator. The primary endpoint was the disease control rate; secondary endpoints were the objective response rate, progression-free survival, overall survival, and safety outcomes. The baseline serum eotaxin level (a potential predictive biomarker of GV1001) was analyzed. To determine whether an adequate immune response had been induced, a delayed-type hypersensitivity test and a T-cell proliferation test were performed. Results: From May 13, 2015 to October 13, 2020, 56 patients with recurrent or metastatic colorectal cancer treated in seven hospitals of South Korea were enrolled. The median patient age was 64 years (range, 29-82 years); 67.9% were men. Of all patients, 66.1% had left-side colorectal cancer and the RAS mutation was present in 25%. The disease control rate and the objective response rates were 90.9% (95% confidence interval [CI]: 82.4-99.4%) and 34.1% (95% CI, 20.1-48.1%), respectively. The median progression-free survival was 7.1 months (95% CI, 5.2-9.1 months) and the median overall survival was 12.8 months (95% CI, 9.9-15.8 months). The most common all-grade adverse events were neutropenia (48.2%), nausea (26.8%), neuropathy (25.0%), stomatitis (21.4%), and diarrhea (21.4%). Immune response analysis showed that no patient had positive delayed-type hypersensitivity test results; antigen-specific T-cell proliferation was observed in only 28% of patients. The baseline eotaxin level was not associated with any efficacy outcome. Conclusion: Although no clear GV1001-specific immune response was observed, the addition of GV1001 vaccination to chemotherapy was tolerable and associated with modest efficacy outcomes.

Prognostic model in patients with metastatic urothelial carcinoma receiving immune checkpoint inhibitors after platinum failure.

Immune checkpoint inhibitors (ICIs) have become a standard treatment for metastatic urothelial carcinoma (mUC) after platinum-based chemotherapy. However, the prognostic factors for patients with mUC receiving ICIs are not well established. We retrospectively collected clinical and laboratory data and reviewed the survival outcomes of patients with mUC who were treated with ICIs after platinum-based chemotherapy. We used univariate and multivariable Cox proportional hazard models to identify independent prognostic factors, and the concordance index (C-index) to evaluate the performance of the new prognostic model. In addition, bootstrap analysis was employed for internal validation of the prognostic model. A total of 224 patients were included in the study. With a median follow-up of 10.5 months (interquartile range, 5.1-17.4 months), median overall survival (OS) was 13.6 months (95% confidence interval [CI], 9.7-17.3 months). In multivariable analysis, independent prognostic factors predicting adverse OS were the presence of liver metastasis (LM), hypoalbuminemia, and neutrophil-lymphocyte ratio (NLR) >5. When patients were categorized into 3 risk groups, median OS was not reached (NR) (95% CI, 17.3-NR), 9.5 months (6.8-NR), and 2.9 months (2.3-4.4) for patients with a score of 0, 1, and 2+, respectively. The C-index for the new model was 0.763 (95% CI, 0.739-0.787). A novel prognostic model, including LM, hypoalbuminemia, and NLR, was developed and validated to estimate OS in patients with platinum-refractory disease on second- or subsequent-line ICI therapy. Further investigations, including prospective validation, are needed.

Disruption of bis leads to the deterioration of the vascular niche for hematopoietic stem cells.

The stem cell niche plays an important role in the microenvironmental regulation of hematopoietic stem cells, but the integration of niche activity remains poorly understood. In this study, we show that a functional deficiency of Bis/BAG-3/CAIR-1, a protein related to apoptosis and the response to cellular stress, results in perturbation of the vascular stem cell niche, causing a series of hematopoietic derangements. Mice with a targeted disruption of bis (bis(-/-)) exhibited a loss of hematopoietic stem cells and defective B-cell development. However, this hematological defect of bis(-/-) mice was not reproduced when bis(-/-) bone marrow cells were transplanted into bis(+/+) recipients. Moreover, bis(+/+) bone marrow cells, when transplanted into bis(-/-) mice, reproduced the same defect as bis(-/-) cells, pointing to the microenvironmental origin of the phenotypes. Subsequent analysis of bis(-/-) mice bone marrow revealed a characteristic defect in the vascular stem cell niche that included the defective growth of stromal progenitor cells in colony forming unit-fibroblasts, the defect in sinusoidal endothelium, and the loss of stromal cells expressing CXCL-12 or IL-7 in the bone marrow. In contrast, no abnormalities were observed in the growth and hematopoietic supporting activities of osteoblasts from bis(-/-) mice bone marrows. Collectively, these results indicate that Bis functions to mediate cellular regulation of the stem cell niche on the vascular compartment and suggest that the vascular and osteoblastic compartments of the stem cell niche can be independently regulated during the in vivo orchestration of hematopoiesis.