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Biomedical subjects

T Katsumata

Publications and source records attributed to T Katsumata.

At least 19 recordsLinked to original sources

Infant partial left ventriculectomy for failure to wean from cardiopulmonary bypass.

Following aortic reimplantation of anomalous left coronary artery from the pulmonary artery in a 6-month-old infant, the heart failed to wean after prolonged supportive cardiopulmonary bypass and maximal inotropic support. We performed partial left ventriculectomy (Batista procedure) that halved left atrial pressure and enabled discontinuation of bypass. Postoperative recovery was then uneventful.

Cardiopulmonary Bypass↗

Is there a relationship between cognitive dysfunction and systemic inflammatory response after cardiopulmonary bypass?

BACKGROUND: The systemic inflammatory reaction (SIR) is assumed to be one of the factors that causes cerebral dysfunction after cardiopulmonary bypass (CPB). The aim of the present study was to evaluate the relationship between the SIR and postoperative cognitive performance at 5 days and 3 months. METHODS: One hundred patients undergoing coronary artery bypass grafting were studied. Inflammatory markers and markers of coagulation and fibrinolysis were determined at several time points during and after the operation. Correlation analysis between maximum levels of the different markers and early and late performance was performed. RESULTS: No overall association was found between the maximum levels of the inflammatory markers and early and late function. CONCLUSIONS: Notwithstanding limitations of statistical power established markers of systemic inflammatory reaction showed no relationship with outcome at 5-day or 3-month follow-up in this subset of patients.

Aged↗

Cbfa1, an essential transcription factor for bone formation, is expressed in testis from the same promoter used in bone.

Cbfa1 is an essential transcription factor for bone formation, but its transcripts have also been detected in thymus and testis. To elucidate the expression of Cbfa1 in testis, we isolated Cbfa1 cDNA from mouse testis. First we examined the length of the transcripts expressed in mouse testis by Northern hybridization. Using a cDNA probe that can detect both Type-I and Type-II Cbfa1 (Type-I: originally reported as Pebp2alphaA by Ogawa et al.; Type-II: originally reported as til-1 by Stewart et al.), 1.8-kb transcripts were detected in testis, and larger transcripts (6.3 kb and 7.4 kb) in T-cell lines, thymus and bone. Using a Type-II specific probe (bone isoform-specific probe), surprisingly, 1.8-kb testis transcript(s) were detected as well as those (6.3 kb) found in bone. In addition, the transcription start site in mouse testis coincides with one of three start sites identified in bone. These results suggest that the testis transcript is generated from the same promoter of Type-II Cbfa1, which is thought to be active only in osteoblasts and some chondrocytes. Next, to define the difference in length of transcripts, we isolated the Cbfa1 cDNA from mouse testis. Sequence analysis of the cDNA showed that alternative splicing around exon 2 and poly-adenylation within exon 8 occurred in the testis isoform, which produce the smaller transcripts. These data revealed that testis Cbfa1 mRNA is transcribed from same promoter used in bones, but the post-transcriptional regulation is different between testis and skeletal tissues.

Animals↗

Mediastinal false aneurysm after thoracic aortic surgery.

BACKGROUND: Postoperative mediastinal false aneurysm is associated with a substantial morbidity and mortality. Surgical treatment is mandatory, although the individual approach varies according to the type of pathologic process, infection status, and site of origin of the aneurysm. METHODS: Between April 1993 and February 1999, we treated 10 patients, aged 25 to 73 years, with anastomotic mediastinal false aneurysm originating from the proximal thoracic aorta. Nine had undergone prior operations on the ascending aorta (7, type A dissection repair; 1, aortitis; 1, root abscess) with a Dacron conduit (n = 5) or valved conduit (n = 4). The last patient had undergone valve replacement for excavating aortic root sepsis. False aneurysms were detected from 2 to 70 months after the most recent operation. Three patients had positive tissue cultures. The surgical procedure was direct suture repair of the disrupted anastomosis in 5, root or ascending aortic replacement with an aortic homograft in 4, and Dacron graft interposition in 1. Hypothermic low-flow perfusion with or without circulatory arrest was used in all patients. RESULTS: There was one hospital death caused by staphylococcal mediastinitis. A false aneurysm recurred after direct suture repair in 2 patients with underlying type A dissection or aortitis. This resulted in one late death. One patient experienced a neurologic event during removal of an infected vascular graft. All 8 surviving patients are alive and well after a mean follow-up of 2 years. Three patients with mycotic false aneurysms remain free from infection after aortic homograft replacement. CONCLUSIONS: Mediastinal false aneurysms are surgically taxing. Low-flow hypothermic perfusion with or without circulatory arrest allows safe reentry. Radical surgery provides a satisfactory outcome in infected patients. Local repair of suture dehiscence in pathologic tissues may predispose to recurrence. We suspect that excessive use of formalin in gelatin-resorcin-formol glue may predispose to tissue necrosis.

Adult↗

Mechanical bridge to recovery in fulminant myocarditis.

A patient with acute fulminant lymphocytic myocarditis and cardiogenic shock was successfully treated by mechanical off loading of the left ventricle. A nonpulsatile left-heart bypass was undertaken with an implantable centrifugal blood pump. Careful weaning resulted in device removal on the seventh day. Left and right ventricular function is sustained at 7 months. Widespread application of this method depends on the availability of an inexpensive user friendly blood pump, appropriate weaning protocols and emerging strategies to promote sustainable myocardial recovery.

Adult↗

Survival advantage of stentless aortic bioprostheses.

BACKGROUND: Bioprostheses (BPs) are used to avoid anticoagulation after aortic valve replacement (AVR) in patients over 65 years of age. Stentless BPs offer established hemodynamic benefits. We sought to determine whether these advantages translate into improved survival. METHODS: Between 1993 and 1997, follow-up data (for Food and Drug Administration submission) were collected prospectively for 160 consecutive, unselected hospital survivors who received the Freestyle valve (FS). Equivalent data were collected for 247 Carpentier-Edwards (CE) porcine xenograft patients. Detailed comparative statistical analysis was used to compare events and survival between the groups. Follow-up was 100% complete for the FS (5.2 years maximum; mean 3.2+/-1.0 years) group and 98% (7.2 years maximum; mean 3.8+/-2.0 years) for CE. RESULTS: The groups were well matched in age (FS, 73+/-6 years; CE, 74+/-6 years), gender (FS, 58% male; CE, 62% male), ventricular function, and number of patients requiring coronary grafts (FS, 41%; CE, 37%). Actuarial survival at 5 years was 84% for FS versus 69% for CE (p = 0.023 Kaplan Meier, p = 0.009 Cox). Annual mortality rates were 3.6% for FS versus 7.1% for CE (p = 0.001). Thromboembolic rate was 0.8% per year for FS and 2.4% for CE (p = 0.024) without a difference in cardiac rhythm. Incidence of nonstructural dysfunction (paravalvular leak) was 0.2% for FS versus 1.3% for CE (p = 0.020). CONCLUSIONS: By 5 years, the stentless valve patients had improved survival and reduced adverse events. Though differences in durability are yet to be proved, our findings support the use of stentless bioprostheses in this age group.

Adult↗

Is there a relationship between serum S-100beta protein and neuropsychologic dysfunction after cardiopulmonary bypass?

OBJECTIVES: Over the past decade, the glial protein S-100beta has been used to detect cerebral injury in a number of clinical settings including cardiac surgery. Previous investigations suggest that S-100beta is capable of identifying patients with cerebral dysfunction after cardiopulmonary bypass. Whether detection of elevated levels S-100beta reflects long-term cognitive impairment remains to be shown. The present study evaluated whether perioperative release of S-100beta after coronary artery operations with cardiopulmonary bypass could predict early or late neuropsychologic impairment. METHODS: A total of 100 patients undergoing elective coronary bypass without a previous history of neurologic events were prospectively studied. To exclude noncerebral sources of S-100beta, we did not use cardiotomy suction or retransfusion of shed mediastinal blood. Serial perioperative measurements of S-100beta were performed with the use of a new sensitive immunoluminometric assay up to 8 hours after the operation. Patients underwent cognitive testing on a battery of 11 tests before the operation, before discharge from the hospital, and 3 months later. RESULTS: No significant correlation was found between S-100beta release and neuropsychologic measures either 5 days or 3 months after the operation. CONCLUSION: Despite using a sensitive immunoluminometric assay of S-100beta, we found no evidence to support the suggestion that early release of S-100beta may reflect long-term neurologic injury capable of producing cognitive impairment.

Anesthesia, General↗

Aortic root replacement with coronary button re-implantation: low risk and predictable outcome.

OBJECTIVE: Cardiac morbidity in aortic root replacement often occurs through myocardial ischaemia. We analyzed a 10 year experience of all root replacement operations by one surgeon to determine the incidence of coronary complications and risk factors for early mortality. METHODS: The study included 140 aortic root replacement patients (aged from 2 to 77 years; median 53 years) operated between 1988 and 1999. Thirty-four had Marfan's syndrome. Eleven had root infection requiring homograft replacement. Nineteen were reoperations (14%). Concomitant procedures were arch replacement (16), mitral replacement (five), and coronary bypass (22). Mobilization and reimplantation of the coronary ostia was performed in 139 patients. We performed the distal graft anastomosis before right coronary reimplantation. RESULTS: There were eight hospital deaths (5.7%). Risk factors for hospital mortality were: preoperative NYHA class IV, shock, LVEF < or =30%, acute dissection, concomitant mitral valve replacement, pump time > or = 60 min, reentry for bleeding, and postoperative renal failure. Neither myocardial ischaemia nor right ventricular dysfunction contribute to mortality. There were 18 late deaths with an actuarial survival of 79% at 5 years. There were no late coronary false aneurysms. CONCLUSIONS: Button reimplantation with the sequence described is predictable and safe. Wrap-around is unnecessary. Coronary aneurysms have been eliminated.

Actuarial Analysis↗

Additive effects of combined treatment with etidronate and alfacalcidol on bone mass and mechanical properties in ovariectomized rats.

The present study was undertaken to evaluate the effects of combined treatment with intermittent cyclical etidronate and daily alfacalcidol on the mass and the mechanical properties of bone in ovariectomized rats, and to compare the effects with those of single treatments. Seventy 14-week-old female rats underwent ovariectomy (ovx) or sham operation, and were assigned to seven groups (n = 10 each): sham-operated; ovx; ovx treated with etidronate; ovx treated with 0.1 microg/kg alfacalcidol; ovx treated with 0.2 microg/kg alfacalcidol; ovx treated with etidronate and 0.1 microg/kg alfacalcidol; and ovx treated with etidronate and 0.2 microg/kg alfacalcidol. One week after the operation, etidronate (4 mg/kg per day) was intermittently injected into rats for 2 weeks followed by a 10 week period of no treatment, and alfacalcidol was administered orally every day. After 24 weeks of treatment, all single and combined treatments increased the bone mineral densities (BMDs) of the proximal tibiae, midfemurs, and the fourth and fifth vertebral bodies, which had been decreased by ovx. Combined treatment groups showed higher BMDs than single treatment groups, and the effects were almost equal to the addition of those of respective single treatment groups. The combined treatment also showed additive effects on the mechanical properties of both midfemurs and L4 vertebral bodies. The increases in mechanical properties were proportional to those in BMDs. Analyses of microcomputed tomography images and histology confirmed the strong effects of combined treatments on both trabecular and cortical bone mass without impairment of mineralization or connectivity. We conclude that the combined treatment with etidronate and alfacalcidol additively increases the mass of bone with normal quality, resulting in bone strengthening in ovx rats.

Animals↗

Hyperparathyroidism is augmented by ovariectomy in Nagase analbuminemic rats.

The role of albumin in bone metabolism was studied in Nagase analbuminemic (NA) rats. Serum calcium (Ca), inorganic phosphate (Pi) and magnesium (Mg) concentrations did not differ between female NA and control Sprague-Dawley (SD) rats at the time of ovariectomy (ovx), although serum ionized Ca was significantly lower in NA rats than in SD rats. Serum parathyroid hormone (PTH) and osteocalcin (OC) concentrations and urinary Ca excretion were significantly greater in NA rats than in SD rats, suggesting hyperparathyroidism and the resultant enhanced bone turnover in NA rats. Paradoxically, ovx increased serum PTH and OC in NA rats but not in SD rats. Ovx-induced exacerbation of hyperparathyroidism was confirmed by significantly greater conversion of 25-hydroxyvitamin D to 1, 25-dihydroxyvitamin D in ovx NA rats even after normalization to vitamin D-binding protein. Bone mineral density (BMD) in proximal tibia increased similarly in a time-dependent manner in sham-operated NA and SD rats. However, ovx ablated the time-dependent increase of BMD in SD rats and significantly decreased BMD in NA rats by 2 wk after ovx, resulting in a significantly lower BMD in ovx NA rats than in ovx SD rats. In summary, NA rats, which are analbuminemic with compensatory increases in lipid and protein synthesis, developed hyperparathyroidism, possibly due to an increase in serum Pi and a reduction of ionized Ca, and ovx induced a greater BMD reduction in NA rats than in SD rats, probably by exacerbating hyperparathyroidism.

Albumins↗

Tissue distribution and pharmacological potential of SM-16896, a novel oestrogen-bisphosphonate hybrid compound.

Postmenopausal osteoporosis is caused mainly by a deficiency of oestrogen with rapid bone loss. To target oestrogen to the bone effectively, we have synthesized and evaluated the effects of a novel hybrid compound of oestrogen and bisphosphonate, SM-16896. The tissue distribution pattern and pharmacological potential are reported. Although the affinity for calf uterine oestrogen receptor was very low (IC50: 73.3 microM; 1/25000 of that of 17beta-oestradiol (2.84 nM)), SM-16896 showed oestrogenic activity. SM-16896 (1 microM) induced a 4.5-fold transcriptional activity in rat osteosarcoma UMR-106 cells compared with vehicle-treated control, when we used the expression vector for human oestrogen receptor and a CAT reporter plasmid containing an oestrogen-responsive element. The distribution of SM-16896 after a subcutaneous administration to 7-week-old female rats was examined by radioluminography using 3H-labelled SM-16896. At 30 min after the administration, significant radioactivity was detected in the bone. At 24 h after administration, a high level of radioactivity was detected in the bone, but in the uterus it was only at a background level. Daily subcutaneous administration of 0.5 mgkg(-1) SM-16896 for 12 weeks (five times per week) to 13-week-old ovariectomized rats suppressed the ovariectomized-induced reduction in bone mineral density. A bone mineral density ratio of 120% was maintained compared with sham-operated rats, whereas a relatively low suppression of uterine weight was observed (about 50% loss compared with sham-operated rats). In the same experiment, the implantation of a 17beta-oestradiol time-release pellet (0.25 mg/pellet/90 days) almost completely suppressed the reduction of both the bone mineral density and uterine tissue weight. It is likely that the effect of SM-16896 on bone was due to its oestrogenic activity, since 1.0 mgkg(-1) SM-18108, the bisphosphonate moiety of this compound, had no effect on bone in 7-week-old ovariectomized rats. The results suggest that SM-16896, a bisphosphonate-conjugated oestrogen, showed a preference profile in the uterus and bone due to its characteristic distribution pattern compared with the natural oestrogen analogue 17beta-oestradiol. Thus, bisphosphonate-conjugated oestrogens have the potential to improve patient compliance in oestrogen therapy by minimizing adverse effects and reducing the frequency of medication.

Animals↗

In vivo NMR micro-imaging of kidney and liver of mouse at 9.4 T.

NMR micro-images of the kidney and liver were measured at 9.4 T in intact mouse, schistosoma Mansoni-infected mouse, and lupus nephritis in an MRL/lpr mouse. High-field NMR imaging has the advantages of sensitivity, spatial resolution, and tissue contrasts based on longitudinal and transverse relaxations, magnetic susceptibility differences and blood flow.

Animals↗

Short report: possible Cryptosporidium muris infection in humans.

Oocysts of cryptosporidia whose morphology resembled that of Cryptosporidium muris were found in the stool of 2 healthy girls in Surabaya, Indonesia. The oocysts were predominantly oval and measured 7.75+/-0.17 x 5.55+/-0.13 microm (mean+/-SD). The number of oocysts excreted were more than 10(5) per gram of stool. The oocysts were well stained with fluorescein-conjugated monoclonal antibody to Cryptosporidium. The specimens from both girls containing the oocysts showed a positive result by the polymerase chain reaction (PCR) using primers specific for the genus Cryptosporidium, but a negative result by the PCR using primers specific for C. parvum. The 2 girls passed oocysts for 5 and 6 days, respectively. They did not complain of any symptoms during the passage of oocysts.

Animals↗

Decrease in protein kinase and phosphatase activities in the liver nuclei of rats exposed to carbon tetrachloride.

The alteration in protein kinase and phosphatase activities in the liver nuclei of rats administered carbon tetrachloride (CCl(4)) was investigated. Rats received a single oral administration of CCl(4) (1 ml/100 g body wt of 5, 10, and 25% CCl(4) in corn oil), and 5, 24, and 48 h later they were euthanized by bleeding. The administration of CCl(4) (10 and 25%) caused a significant decrease in protein kinase activity in the liver nuclei. The enzyme activity in the liver nuclei from normal and CCl(4)-administered rats was significantly increased by the addition of Ca(2+) (0.5 mM) and calmodulin (10 microg/ml) in the reaction mixture, suggesting that Ca(2+)/calmodulin-dependent protein kinase activation is not suppressed by CCl(4) treatment. Liver nuclear phosphatase activity toward phosphotyrosine, but not phosphoserine and phosphothreonine, was markedly decreased by CCl(4) (5, 10, and 25%) administration. This decrease was seen 5 h after CCl(4) administration. The presence of vanadate (10(-4) M) in the reaction mixture caused a significant decrease in phosphotyrosine phosphatase activity in the liver nuclei from normal and CCl(4)-administered rats, whereas the enzyme activity was not decreased by okadaic acid (10(-5) M) or sodium fluoride (10(-3) M). The effect of anti-regucalcin antibody (100 ng/ml) in increasing phosphotyrosine phosphatase activity was seen in the liver nuclei of CCl(4)-administered rats, suggesting that regucalcin-sensitive phosphatase activity is decreased by CCl(4) administration. The present study demonstrates that CCl(4) administration induces a decrease in protein kinase and tyrosine phosphatase activities, which are involved in signaling factors in the liver nuclei of rats.

Animals↗

Isolation and characterization of the distal promoter region of mouse Cbfa1.

Cbfa1 is an essential transcription factor for bone formation, and as such little is known about the region responsible for the transcriptional regulation of this gene. Here we report the determination of the transcription start sites, isolation and partial characterization of distal promoter region of this gene. Three transcription start sites were identified by the 5'-Cap site method, recently invented for rapid examination of the 5'-end of genes of interest. A reporter construct containing 1.8 kb of 5' of transcription start sites had approximately 25-fold more luciferase activity than the promoter-less vector in osteoblastic cell lines. Deletion analysis of the reporter construct demonstrated that the minimal region to express promoter activity lies between bp -168 and -99, taking the most downstream transcription start site as +1. By Northern blot analysis, mRNA expression from the distal promoter was detected in the differentiated osteoblastic cell lines, UMR-106, ROS17/2.8 and MC3T3-E1, but not in cell lines of immature phenotype or originated from other organs. Luciferase activity was strongest in UMR-106 and ROS17/2.8, and weakest in COS-1 and HepG2, which are cell lines originating from other organs, corresponding to the level of mRNA expression. These results demonstrated that the distal promoter region examined here is important for tissue- and cell-type-specific gene expression of Cbfa1.

Animals↗

Delayed administration of ethyl eicosapentate improves local cerebral blood flow and metabolism without affecting infarct volumes in the rat focal ischemic model.

The objective of this study was to assess whether delayed administration of ethyl eicosapentate has a favorable effect on cerebral blood flow and metabolism in rats suffering from cerebral infarction. Adult male Sprague-Dawley rats weighing 250-300 g were used. Left middle cerebral artery occlusion was induced for 2 h. After 24-h reperfusion, rats were treated with ethyl eicosapentate (100 mg kg(-1); ethyl eicosapentate treated) or saline (saline treated) by gavage, once a day for 4 weeks. After 4 weeks, local cerebral blood flow and local cerebral glucose utilization were measured autoradiographically, and infarction size was measured. In the ischemic side, the local cerebral blood flow and local cerebral glucose utilization values in the parietal cortex and the lateral caudoputamen, which constituted the ischemic core, were equivalent to zero in both groups. The peri-infarcted areas, i.e., the frontal cortex and medial caudoputamen, were significantly higher in the ethyl eicosapentate treated group than the saline treated group. In the non-ischemic side, ethyl eicosapentate treated group had a tendency to improve local cerebral blood flow and local cerebral glucose utilization values in a medial caudoputamen. These results suggest that ethyl eicosapentate treatment may be beneficial for maintaining cerebral circulation and metabolism except for infarction area after cerebral infarction.

Animals↗

Cbfa1 isoforms exert functional differences in osteoblast differentiation.

Cbfa1 is an essential transcription factor for osteoblast differentiation and bone formation. We investigated functional differences among three isoforms of Cbfa1: Type I (originally reported as Pebp2alphaA by Ogawa et al. (Ogawa, E., Maruyama, M., Kagoshima, H., Inuzuka, M., Lu, J., Satake, M., Shigesada, K., and Ito, Y. (1993) Proc. Natl. Acad. Sci. U. S. A. 90, 6859-6863), Type II (originally reported as til-1 by Stewart et al. (Stewart, M., Terry, A., Hu, M., O'Hara, M., Blyth, K., Baxter, E., Cameron, E., Onions, D. E., and Neil, J. C. (1997) Proc. Natl. Acad. Sci. U. S. A. 94, 8646-8651), and Type III (originally reported as Osf2/Cbfa1 by Ducy et al. (Ducy, P., Zhang, R., Geoffroy, V., Ridall, A. L., and Karsenty, G. (1997) Cell 89, 747-754). A reverse transcriptase-polymerase chain reaction analysis demonstrated that these isoforms were expressed in adult mouse bones. The transient transfection of Type I or Type II Cbfa1 in a mouse fibroblastic cell line, C3H10T1/2, induced the expression of alkaline phosphatase (ALP) activity. This induction was synergistically enhanced by the co-introduction of Xenopus BMP-4 cDNA. In contrast, the transient transfection of Type III cDNA induced no ALP activity. In C3H10T1/2 cells stably transfected with each isoform of Cbfa1, the gene expression of ALP was also strongly induced in cells transfected with Type I and Type II Cbfa1 but not in cells with Type III Cbfa1. Osteocalcin, osteopontin,and type I collagen gene expressions were induced or up-regulated in all of the cells stably transfected with each isoform of Cbfa1, and Type II transfected cells exhibited the highest expression level of osteocalcin gene. A luciferase reporter gene assay using a 6XOSE2-SV40 promoter (6 tandem binding elements for Cbfa1 ligated in front of the SV40 promoter sequence), a mouse osteocalcin promoter, and a mouse osteopontin promoter revealed the differences in the transcriptional induction of target genes by each Cbfa1 isoform with or without its beta-subunit. These results suggest that all three of the Cbfa1 isoforms used in the present study are involved in the stimulatory action of osteoblast differentiation, but they exert different functions in the process of osteoblast differentiation.

Animals↗

Markedly elevated cell turnover is characteristic of small, deeply invasive carcinomas of the colorectum.

BACKGROUND: Small, deeply invasive carcinomas invading the muscularis propria or deeper and measuring < or = 2 cm in greatest dimension (S-ADV) are rare in comparison with their larger counterparts (NS-ADV), and their clinicopathologic features are obscure. METHODS: S-ADV and NS-ADV cases as well as cases of submucosal carcinoma (SM-CA) were comparatively assessed for: 1) clinicopathologic findings; 2) Ki-67, mitotic, and apoptotic indices; 3) cathepsin G, p53, and bcl-2 immunoreactivities; and 4) c-Ki-ras mutations. RESULTS: S-ADV and SM-CA, which both are significantly smaller than NS-ADV, did not differ in size, but the frequency of moderately and poorly differentiated carcinoma elements at the leading edges was observed to be higher than in the central cores only in S-ADV, as was tumor "budding" of small clusters of undifferentiated carcinoma cells. The frequency of severe lymphatic involvement in S-ADV was as high as in NS-ADV, and significantly greater than in SM-CA. The Ki-67, mitotic, and apoptotic indices for S-ADV were significantly increased compared with those for NS-ADV and/or SM-CA. Expression of cathepsin G in S-ADV tumor and stromal cells was significantly decreased compared with NS-ADV and/or SM-CA cases. No significant differences in the expression of either p53 or bcl-2 or the incidence of c-Ki-ras mutations were observed among the three groups. CONCLUSIONS: S-ADV can be considered a distinct type of deeply invasive carcinoma, presenting with poor tumor differentiation at the leading edge, and with increased tumor cell proliferation despite its small size.

Biomarkers, Tumor↗