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Go Watanabe

Publications and source records attributed to Go Watanabe.

At least 19 recordsLinked to original sources
PubMed2006

STAT1 activation-induced apoptosis of esophageal squamous cell carcinoma cells in vivo.

BACKGROUND: The induction of apoptosis might be a promising treatment for cancers refractory to conventional therapies, such as esophageal cancer. In this study, we examined whether epidermal growth factor-induced growth inhibition results from apoptosis of esophageal squamous cell carcinoma (SCC) cells as a result of STAT1 activation and evaluated whether interferon gamma (IFN-gamma) can induce apoptosis of cancer cells in vivo. METHODS: To assess the function of STAT1, we established stable transfectants expressing dominant-negative STAT1. Apoptosis was assessed by several experimental techniques, including flow cytometry. Differentiation was evaluated by Western blot test with involucrin used as a marker. In vivo, cancer cells were injected into male BALB/c nu/nu mice. Two weeks later, the mice started to receive injections of IFN-gamma or saline into a tail vein four times per week. Concentrations of IFN-gamma in the tumors were analyzed by enzyme-linked immunosorbent assay. Apoptosis was evaluated by TUNEL (terminal deoxynucleotidyl transferase dUTP nick-end labeling) staining. RESULTS: Epidermal growth factor inhibited the growth of esophageal SCC cells by causing apoptosis through several pathways involving STAT1 activation. IFN-gamma induced the apoptosis of cancer cells, but it also promoted the differentiation (not apoptosis) of primary cultured cells derived from normal esophageal epithelium. IFN-gamma also inhibited the growth of xenograft tumors of esophageal SCC cells in vivo. CONCLUSIONS: Our results suggest that IFN-gamma is one candidate for cytokine-based therapy of cancer. IFN-gamma-induced STAT1 activation might be involved in the apoptosis of esophageal SCC cells and in the terminal differentiation of normal squamous cells. Further studies of STAT1 signaling pathways may provide the basis for new targeted therapeutic strategies for esophageal SCC.

Animals↗
PubMed2006

Mirror glasses for minimally invasive surgery.

INTRODUCTION: The operator performing minimally invasive surgery is prevented from seeing the whole field with both eyes by the restricted small thoracotomy incision. To overcome this problem, we developed mirror glasses. METHODS: Use of these glasses was evaluated in terms of the time required for threading of sutures with endoscopic forceps. Three surgeon ligated thread a suture five times with and without use of the glasses in the box, and the mean time was calculated for each surgeon. RESULTS: The time required for ligation (mean +/- SD) was 24.2 +/- 2.9 s with mirror glasses and 27.0 +/- 2.5 s without the glasses (p = 0.01). CONCLUSION: The mirror glasses may be found useful for fine manipulation for minimally invasive surgery.

Equipment Design↗
PubMed2006

Pharmacogenetic profiling and clinical outcome of patients with advanced gastric cancer treated with palliative chemotherapy.

PURPOSE: To investigate whether polymorphisms with putative influence on fluorouracil/cisplatin activity are associated with clinical outcomes of patients with advanced gastric cancer (AGC). PATIENTS AND METHODS: Peripheral blood samples from 175 prospectively enrolled AGC patients treated with fluorouracil/cisplatin palliative chemotherapy were used for genotyping 13 polymorphisms in nine genes (TS, MTHFR, XPD, ERCC1, XRCC1, XRCC3, GSTPI, GSTTI, GSTMI). Genotypes were correlated to response and survival. RESULTS: The overall response rate was 41%, the median progression-free survival (PFS) was 24 weeks (range, 4 to 50 weeks), and the median overall survival (OS) was 39 weeks (range, 8 to 72+ weeks). Chemoresistance and poor survival were significantly associated with TS 5'-UTR 3G-genotype (2R/3G, 3C/3G, 3G/3G) and GSTP1 105 A/A homozygous genotype. Sixty-one patients (35%) did not show any of these risk genotypes (group 0), 57 patients (32.5%) showed one of the two risk genotypes (group 1), and 57 patients (32.5%) showed both risk genotypes (group 2). Median PFS and OS in group 0 patients were 32 weeks (range, 8 to 50 weeks) and 49 weeks (range, 18 to 72+ weeks), respectively. Group 1 and group 2 patients showed significantly worse PFS (median, 26 weeks [range, 6 to 44 weeks] and 14 weeks [range, 4 to 38 weeks], respectively) and worse OS (median, 39 weeks [range, 10 to 58 weeks] and 28 weeks [range, 8 to 56 weeks]), respectively, than group 0 patients. This adverse effect was retained in multivariate analysis. CONCLUSION: Specific polymorphisms may influence clinical outcomes of AGC patients. Selecting palliative chemotherapy on the basis of pretreatment genotyping may represent an innovative strategy that warrants prospective studies.

Adult↗
PubMed2006

Esophageal cancer: evaluation with triple-phase dynamic CT--initial experience.

PURPOSE: To prospectively assess which phase of a triple-phase dynamic contrast material-enhanced multi-detector row computed tomography (CT) protocol is optimal for visualization of esophageal cancer. MATERIALS AND METHODS: The study was supported by the local ethical committee; all patients gave written informed consent. Thirty-one lesions in 28 consecutive patients (26 men, two women; mean age, 65 years; range, 53-87 years) with histopathologically confirmed esophageal cancer were evaluated with triple-phase dynamic CT performed at 5, 35, and 65 seconds (first arterial, second arterial, and venous phases) after attenuation of 200 HU was obtained at the descending aorta. Qualitative image analysis was performed to assess appearance and conspicuity of the tumor. Appearances of all 31 lesions were classified into three categories-not identifiable, focal enhancement with or without minimal (<1 cm) wall thickening, and focal mass lesion or obvious (>1 cm) wall thickening. Results were compared with surgical or endoscopic ultrasonographic findings. Quantitative assessment included regions-of-interest measurement of the tumor and normal esophageal wall and the difference between those measurements. A paired t test was used to determine which phase showed the highest tumor attenuation and tumor-to-normal esophageal wall attenuation differences. RESULTS: At visual assessment, 30 lesions were identified in the second arterial phase. Of these 30 lesions, eight were focal enhancements; the best conspicuity was during the second arterial phase. Furthermore, seven of these eight lesions were T1 cancers. The remaining 22 lesions were enhanced masses or wall thickening. Twenty-one of these 22 tumors also showed best conspicuity in the second arterial phase. The greatest attenuation of tumors in the second arterial phase was 130.0 HU, and the difference in attenuation between tumor and normal esophageal wall was 50.6 HU in the second arterial phase, which were significantly higher than those in the other two phases (P<.01, each). CONCLUSION: The second arterial phase of dynamic CT is the optimal phase for visualization of esophageal cancer.

Adenocarcinoma↗
PubMed2006

Methylenetetrahydrofolate reductase 677C/T gene polymorphism, gastric cancer susceptibility and genomic DNA hypomethylation in an at-risk Italian population.

We performed a case-control study to examine the relationship between MTHFR C677T gene polymorphism (MTHFR677C/T) and gastric cancer susceptibility in at-risk populations in central Italy. To explore genomic DNA hypomethylation as a potential etiologic mechanism, this phenomenon was evaluated in carriers of the MTHFR677T/T genotype and carriers of the wild-type MTHFR677C/C genotype. Lymphocyte genomic DNA from 162 gastric cancer patients and 164 controls was used for MTHFR677C/T genotyping. Unconditional regression analysis with ORs and 95% CIs was used to investigate the association of the polymorphism with disease. Genomic DNA methylation status by an established enzymatic assay that measures the DNA accepting capacity of methyl groups (inversely related to endogenous methylation) was assessed in a random sample of 40 carriers of the wild-type MTHFR677C/C genotype and 40 carriers of the MTHFR677T/T genotype. The global allelic distribution was in Hardy-Weinberg equilibrium. The MTHFR677T allele was significantly associated with gastric cancer risk with an OR of 2.49 (95% CI 1.48-4.20) in heterozygous MTHFR677C/T carriers and an OR of 2.85 (95% CI 1.52-5.35) in homozygous MTHFR677T/T carriers. This risk association was retained in subgroup analyses by tumor histotype and location. Genomic DNA hypomethylation status in MTHFR677T/T carriers was significantly higher than in subjects with wild-type MTHF677C/C genotype (p = 0.012). In the studied population, MTHFR677T played the role of a moderate-penetrance gastric cancer susceptibility allele. Possession of the MTHFR677T/T genotype was significantly associated with genomic DNA hypomethylation. These findings deserve further investigation in the context of novel strategies for gastric cancer prevention.

Adult↗
PubMed2006

Tissue oxygen saturation during colorectal surgery measured by near-infrared spectroscopy: pilot study to predict anastomotic complications.

INTRODUCTION: We investigated the relation between tissue oxygen saturation measured by near-infrared spectroscopy (NIRS) and anastomotic complications associated with colorectal surgery. METHODS: A series of 20 patients with colorectal cancer underwent radical surgery with enteric anastomosis. Measurements of tissue oxygen saturation (StO2) were performed at both the proximal and distal portions of the anastomotic site; in cases of anterior resection, we measured StO2 only in the proximal portion. RESULTS: Two anastomotic complications (one leakage, one stenosis) occurred in the 20 cases. The StO2 in patients with anastomotic complications was 58.0%, and that in patients without complications was 71.0%. Altogether, 18 patients had StO2 values > 66%, and none of them had anastomotic complications. In contrast, 2 patients had StO2 values < 60%, and both had anastomotic complications. CONCLUSIONS: The StO2 of the anastomotic site can be safely and reliably measured by NIRS during colorectal surgery. Low StO2 on both sides of the anastomosis may indicate an increased risk of anastomotic complications. Further study is needed to determine the cutoff value for StO2 required to prevent serious complications.

Aged↗
PubMed2006

Retrospective analysis of 45 consecutive patients with advanced gastric cancer treated with neoadjuvant chemotherapy using an S-1/CDDP combination.

BACKGROUND: Standard treatment for highly advanced gastric cancer (AGC) has not been established yet. Neoadjuvant chemotherapy (NAC) represents a promising approach, which may improve the prognosis of AGC. In this study, we analyzed the feasibility and efficacy of NAC with S-1 (TS-1)/cisplatin CDDP in order to design appropriate clinical trials for AGC. METHODS: Results for a series of 45 consecutive patients with AGC treated with S-1/CDDP induction chemotherapy since January 2002 were analyzed retrospectively. RESULTS: The primary tumor was resected in 36 of the 45 patients (resectability, 80.0%). Progression of the disease during chemotherapy was observed in 1 patient only (2.2%). No treatment-related deaths occurred, and serious adverse effects (grade 3-4) were noted in only 2.2% of the patients. The overall median survival time was 1.82 years. Especially noteworthy is that, in patients with highly advanced disease (pretreatment [c]-stage IV; n = 27), resectability was 66.7% and curative (R0) resection was possible in 10 patients. The median survival times for c-stage IV patients who had total, curative, and noncurative resections were 20.8, 22.3 and 12.6 months, respectively. R0 resection was possible for all c-stage III patients (n = 17), with a 2-year overall survival of 90.9%. The downstaging rate was 55.6% (20/36), resulting in a significantly improved prognosis for the downstaged patients (P = 0.012). CONCLUSION: Induction chemotherapy using S-1/CDDP for AGC appears to be a safe and promising treatment. We have therefore started two independent multiinstitutional clinical trials to evaluate the efficacy of this treatment.

Aged↗
PubMed2006

Portable coronary active perfusion system for off-pump coronary artery bypass grafting.

PURPOSE: The present study was performed to develop a new perfusion system for off-pump coronary artery bypass grafting and to examine whether even a simple coronary perfusion system can maintain adequate blood flow delivery during anastomosis. DESCRIPTION: The experiment was performed in two stages. In procedure 1, 3 pigs with left anterior descending artery occlusion were used to evaluate optimal perfusion flow rate and coronary artery internal pressure, and to evaluate the safety area of perfusion. In procedure 2, 6 pigs were used to validate the new portable coronary perfusion system. EVALUATION: The optimal blood flow in the portable coronary active perfusion system was less than approximately 40 mL/min. The small, easy to use pump system (ie, the portable coronary active perfusion system) may prevent hemodynamic deterioration and ventricular arrhythmia during coronary occlusion, resulting in better maintenance of left ventricular function. CONCLUSIONS: Even a simple pump system can achieve effective perfusion for safe anastomosis. Further studies are required to allow the clinical use of this system.

Anastomosis, Surgical↗
PubMed2006

Hybrid surgical angiogenesis: omentopexy can enhance myocardial angiogenesis induced by cell therapy.

BACKGROUND: The conditions at the injection site are important in cell transplantation for severe ischemic heart disease. The omentum is both a well-vascularized tissue and a source of angiogenic factors. We examined the effectiveness of autologous bone marrow-derived mononuclear cells (BM-MNCs) with or without omentopexy in a large animal model. METHODS: Myocardial infarction was generated in the lateral wall by ligation of coronary artery branches in miniswine. Animals received BM-MNC injection with or without omentopexy. Controls received saline only. Three weeks after surgery, regional myocardial blood flow and contractility were measured, and density of arterioles was evaluated immunohistologically. Angiography and postmortem examinations were performed to determine collateral communication. RESULTS: Regional myocardial contractility was significantly improved by BM-MNC transplantation both with and without omentopexy (0.29 +/- 0.02 vs 0.11 +/- 0.03, p < 0.01, 0.30 +/- 0.02 vs 0.12 +/- 0.01, p < 0.01, respectively). Relative regional myocardial blood flow in the combined omentopexy group was significantly higher than the controls both at rest (1.05 +/- 0.11 vs 0.57 +/- 0.07, p < 0.01) and under stress (1.09 +/- 0.08 vs 0.40 +/- 0.10, p < 0.01). The number of arterioles (< 50 microm) in both groups were higher than the controls (88.1 +/- 5.00 vs 38.1 +/- 8.99, p < 0.01 and 109.2 +/- 9.91 vs 38.1 +/- 8.99, p < 0.01, respectively). The number of large arterioles (> 50 microm) in the combined omentopexy group was significantly higher than in both BM-MNC alone (26.9 +/- 2.4 vs 17.6 +/- 1.8, p = 0.011) and controls (26.9 +/- 2.4 vs 10.0 +/- 1.3, p < 0.01). Collateral communication between the omentum and myocardium was demonstrated by angiography and postmortem injection. CONCLUSIONS: The BM-MNC transplantation may attenuate cardiac contractile dysfunction, and omentopexy may enhance angiogenesis induced by BM-MNC transplantation.

Angiography↗
PubMed2006

Results of initial operations in non-small cell lung cancer patients with single-level N2 disease.

BACKGROUND: There is still debate regarding the use of surgery in the management of non-small cell lung cancer patients with N2 disease. The primary aim of the present study was analysis of the results of initial operations in non-small cell lung cancer patients with single-level N2 disease. METHODS: Ninety-four patients with the disease who underwent initial surgery consisting of complete resection of the primary site plus systematic lymphadenectomy were examined. We also immunohistochemically examined lymphatic vessel density and vascular endothelial growth factor-C expression. RESULTS: The overall 5- and 10-year survival rates for the 94 patients were 27.1% and 12.1%, respectively, with a median survival of 22 months. When stratified by skipping status, the 5-year survival rates for the patients in skip-N2 and non-skip-N2 groups were 33.4% and 19.8%, respectively (p = 0.0189). Skip metastasis, T factor, subcarinal lymph node metastasis, and adjuvant chemotherapy were recognized as independent prognostic indicators. In both skip-N2 and non-skip-N2 groups, distant relapse was the dominant pattern of recurrence. Although the peritumoral lymphatic vessel density was associated with vascular endothelial growth factor-C expression in tumors, the lymphangiogenic profile appeared to be different between skip-N2 and non-skip-N2 tumors, suggesting different nodal metastatic process. CONCLUSIONS: Lung cancer patients with single-level N2 disease are an oncologically heterogeneous cohort. Although further studies involving randomized comparisons are required, the poor outcomes found here indicate that the initial operation has yet to be validated for patients with this disease.

Adult↗
PubMed2006

Pathologic and biological assessment of lung tumors showing ground-glass opacity.

BACKGROUND: We evaluated the pathologic and biological aspects of lung tumors 3.0 cm or less in diameter with the appearance of ground-glass opacity (GGO). METHODS: Of 988 patients with non-small cell lung cancer who underwent operations at our institute between January 1994 and December 2004, 87 resected lung tumor specimens that showed GGO appearance on helical computed tomography were obtained from 81 patients. Forty-four lesions were pure GGO with no solid component in the tumor and 43 lesions were mixed GGO consisting of areas of attenuation with a solid component. Together with histological features, MIB1 and nm23 expression within tumors were examined immunohistochemically. RESULTS: The mean tumor size in the pure GGO group was significantly smaller than that in the mixed GGO group. The composition of pathologic subtypes and biological characteristics were clearly different between the two groups. Although atypical adenomatous hyperplasia and localized bronchioloalveolar cell carcinoma of Noguchi's A and B were the predominant pathologic subtypes and nm23 negativity was rare in the pure GGO group, a high score for expression of MIB1 was often found in pure GGO tumors even though the tumors were less than 10 mm in diameter. CONCLUSIONS: If the tumor is 2 cm or less in diameter, the ability of invasion and metastasis seems to be low in pure GGO tumors. However, the proliferation ability of these tumors suggests the necessity of a careful follow-up schedule if the tumor is greater than 5 mm in diameter. For mixed GGO tumors, surgical resection instead of observation is justified.

Carcinoma, Non-Small-Cell Lung↗
PubMed2006

Successful coronary revascularization using the PAS-Port system in a patient with Takayasu's arteritis and Behcet's disease.

Coronary artery disease is rare in patients with Takayasu's arteritis or Behcet's disease. We report the case of a patient with concomitant Takayasu's arteritis and Behcet's disease who had angina pectoris develop due to severe narrowing of the left main coronary artery. The patient underwent revascularization with saphenous vein grafts with the assistance of the PAS-Port Proximal Anastomosis System (Cardica, Inc, Redwood City, CA). In conclusion, the PAS-Port Proximal Anastomosis System seems to be a safe and effective method of facilitating revascularization, particularly when severe calcification of the ascending aorta precludes cross-clamping during off-pump coronary artery bypass grafting.

Anastomosis, Surgical↗
PubMed2006

Surgical results in T2N0M0 nonsmall cell lung cancer patients with large tumors 5 cm or greater in diameter: what regulates outcome?

BACKGROUND: We assessed the surgical results along with the clinical and biological features of nonsmall-cell lung cancer (NSCLC) patients with localized large tumors. METHODS: The study population consisted of 86 NSCLC patients who underwent complete resection of tumors 5 cm or larger in diameter in stage IB (T2N0M0). We immunohistochemically assessed the expression of angiostatin and endostatin. RESULTS: The median tumor size was 6.0 cm (range, 5 to 14 cm). The operative procedures used were lobectomy in 71 cases, bilobectomy in 8 cases, and pneumonectomy in 11 cases. Fifty patients (58.1%) relapsed during the mean follow-up period of 33.6 +/- 4.5 months. The median disease-free interval was 9 months. Of 44 recurrent patients whose disease-free interval could be identified, 25 patients (56.8%) relapsed within 12 months after the operation. The overall 5- and 10-year survival rates were 42.0% and 24.2%, respectively. Multivariate analysis showed that the degree of pleural involvement and angiostatin expression within the tumor were independent prognostic indicators. The endostatin expression within tumors also had a weaker relationship with outcome. CONCLUSIONS: Long-term surgical results were poor and early relapse was common in this cohort. In addition to pleural involvement, the tumor-induced expression of angiostatin and endostatin merit further investigation to gain possible insights into selection of patients who will benefit from surgery as the first line treatment.

Aged↗
PubMed2006

Robotic replacement of the descending aorta in human cadaver.

Robot-assisted replacement of the thoracic aorta was performed in a human cadaver. Temporary shunt bypass was established by inserting a left axillary artery catheter and directing it through the aortic arch toward the right femoral artery through the abdominal aorta. The technique utilized the da Vinci surgical system inserted through the 4-cm supramammary working port and two additional thoracoscopic ports. The working port allowed the introduction of an endoscope, endoscopic instruments, and artificial graft and suture materials. The aorta was dissected using the robotic instruments and was clamped with two transthoracic clamps. After transaction of the aorta, a 20-mm polytetrafluoroethylene graft was cut and an end-to-end anastomosis was then performed with running 3-0 Prolene sutures with robotic instruments. The robotic system provides superior optics and allows for enhanced dexterity. Minimally invasive robotic replacement of the descending aorta is an effective procedure and may add benefits for both surgeon and patients.

Aorta, Thoracic↗
PubMed2006

An innovative balloon-type surgical device for atrial fibrillation.

BACKGROUND: The maze procedure and its modifications are the surgical treatment for atrial fibrillation. In an attempt to achieve a less invasive operation, we developed a balloon-type device for electric pulmonary vein isolation and evaluated its effectiveness macroscopically and microscopically. METHODS: We created a left heart system model from 20 pigs. Based on a mold, a balloon was made with silicone resin. When this balloon was inflated, all pulmonary vein orifices were pressed and ablated by probes using radiofrequency and cryotherm as energy sources. Macroscopic and microscopic evaluations were performed. RESULTS: Complete circular ablation by radiofrequency was confirmed in 2 of 3 veins. The transmural denaturation was pathologically confirmed in all areas ablated at 80 degrees for 2 minutes. The complete circular ablation line and the transmural denaturation were macroscopically and microscopically confirmed after cryoablation at -100 degrees for 2 minutes using liquid nitrogen. CONCLUSIONS: This study proved that the balloon is effective in simplifying pulmonary vein isolation and has potential to become an instrument that contributes to less invasive operations in the near future.

Animals↗
PubMed2006

In vitro sensitivity to platinum-derived drugs is associated with expression of thymidylate synthase and dihydropyrimidine dehydrogenase in human lung cancer.

Thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) are critical enzymes in nucleic acid metabolism. Proliferating cell nuclear antigen (PCNA) is a specific protein that is correlated with proliferative activity of cells. The TS gene has a variable number of tandem repeats (VNTR) in its 5'-untranslated region and a single nucleotide polymorphism (SNP) in the VNTR area. We examined the association of in vitro sensitivity to anticancer drugs with TS polymorphism, TS, DPD, and PCNA mRNA expression using human lung cancer tissues. Seventy-eight surgically resected lung cancer tissues were tested for in vitro sensitivity to 5-fluorouracil, cisplatin (CDDP), carboplatin (CBDCA), irinotecan, docetaxel, and gemcitabine by histoculture and MTT assay. The TS polymorphisms were analyzed by PCR and PCR-RFLP. TS, DPD, and PCNA mRNA expression levels were quantified by real-time RT-PCR and normalized relative to beta-actin mRNA expression. The inhibition rates (IRs) of CDDP and CBDCA were significantly correlated with TS/PCNA, the ratio of TS/actin and PCNA/actin, and DPD/PCNA, the ratio of DPD/actin and PCNA/actin. This correlation was further explored by subgroup analyses according to TS VNTR or TS functional type, in which 2R/3G, 3C/3G, or 3G/3G were classified into H-type group and 2R/2R, 2R/3C, or 3C/3C into L-type group. The associations of TS/PCNA and DPD/PCNA with the IRs of CDDP, CBDCA remained significant in the 3R/3R group and H-type group. These results suggest that in vitro sensitivity to platinum-derived drugs, CDDP and CBDCA, is associated with PCNA-normalized mRNA expression of TS and DPD in human lung cancer tissues, as affected by the TS polymorphism. The clinical significance of these pharmacogenomic markers for chemotherapy regimens with platinum-derived drugs should be investigated further for personalized treatment of lung cancer.

Adult↗
PubMed2006

[Endoscopic off-pump coronary artery bypass].

Since 1999, we have performed total endoscopic off-pump coronary artery bypass (OPCAB). Innovation of endoscopic optic techniques and development of endoscopic forceps were necessary to perform this procedure. The operative methods of the endoscopic OPCAB; a 12 mm port for 3-D endoscope is firstly inserted through the 5th intercostal space (ICS) in the mid axillary line, and then the left internal thoracic artery (LITA) is taken down in semi-skeletonized fashion using other 2 instrumental 5 mm ports (the 3rd, 6th anterior axillary ICS). To anastomose LITA to the left anterior descending artery (LAD), other 2 10 mm and 12 mm ports are inserted through the 4th ICS in parallel. A conventional end-to-side anastomosis is manually performed with 8-0 prolene. The average LITA harvesting time and anastomotic time have been shortened significantly thanks to the endoscopic innovation. However, there are some limits to manual manipulations in the endoscopic OPCAB. Robotic surgery might have more advantages to the flexibility of forceps tips. The introduction of robotic surgery system is indispensable to safe and certain endoscopic OPCAB.

Coronary Artery Bypass, Off-Pump↗