Biomedical subjects

T Kijima

Publications and source records attributed to T Kijima.

At least 19 recordsLinked to original sources

PubMed2001

Gene therapy utilizing the Cre/loxP system selectively suppresses tumor growth of disseminated carcinoembryonic antigen-producing cancer cells.

Recent clinical trials of cancer gene therapy have shown encouraging results for controlling localized tumors. However, to control metastatic or disseminated tumor cells, further modification of vectors is required to enhance specificity and infectivity against targets. We investigated whether utilization of the Cre recombinase(Cre)/loxP system contributes to enhanced antitumor effects together with minimal adverse reactions in specific gene therapy against disseminated carcinoembryonic antigen (CEA)-producing cancer cells in the peritoneal cavity of mice. CEA-producing cancer would be a good therapeutic target because it is found in lung, stomach and colon sites, which account for most cancers. We constructed a pair of recombinant adenoviral vectors (Ads), one of which expresses the Cre gene under the control of the CEA promoter (Ad.CEA-Cre); the other expresses the herpes simplex virus thymidine kinase (HSV-TK) gene (Ad.lox-TK), or the beta-galactosidase gene (beta-gal) by Cre (Ad.lox-beta-gal). Intraperitoneal coinjection of Ad.CEA-Cre and Ad.lox-beta-gal into mice with peritonitis carcinomatosa by CEA-producing tumor cells showed selective expression of the beta-gal gene in tumor foci. Coinfection of Ad.CEA-Cre and Ad.lox-TK followed by ganciclovir (GCV) administration significantly suppressed the total tumor weight in the peritoneal cavity of the mice to 13% of that of the untreated mice and 22% of that of the mice treated with Ad.CEA-TK/GCV, an Ad that expressed the HSV-TK gene driven by the CEA promoter alone. Moreover, treatment with Ad.CEA-Cre and Ad.lox-TK/GCV completely suppressed tumors in 4 of 10 (40%) mice without significant weight loss, although 2 of 10 mice treated with Ad.CAG-TK/GCV, an adenovirus vector that strongly but nonspecifically expressed the TK gene, died due to severe side effects including diarrhea, weight loss and liver dysfunction. These findings suggest that cell type-specific gene therapy using the Cre/loxP system is effective against disseminated cancer cells without significant side effects.

Adenoviridae↗

PubMed2001

Adenovirus-mediated gene therapy specific for small cell lung cancer cells using a Myc-Max binding motif.

Recent clinical trials of gene therapy for patients with thoracic cancers have shown that these treatments were well tolerated with minimal side effects and that we need to further enhance specificity as well as efficiency of gene transfer to target cancer cells. We previously reported that myc-overexpressing SCLC cell lines became selectively sensitive to ganciclovir (GCV) by transducing the herpes simplex virus thymidine kinase (HSV-TK) gene under the control of the Myc-Max response elements (a core nucleotide sequence, CACGTG) and that this construct (MycTK) could be utilized to develop a novel treatment against chemo-radio-resistant SCLC. We report here in vivo antitumor effects and safety of a replication-deficient adenoviral vector containing the Myc-Max binding motif (AdMycTK) on SCLC cells. In vitro infection with AdMycTK selectively rendered myc-overexpressing SCLC cell lines 63- to 307-fold more sensitive to GCV. In vivo injections with AdMycTK followed by GCV administration markedly suppressed the growth of myc-overexpressing tumors established in the subcutis or in the peritoneal cavity of athymic mice. On the other hand, infection with AdMycTK did not significantly affect either in vitro GCV sensitivity of the cells expressing very low levels of the myc genes or the growth of their subcutaneous tumors. Moreover, we observed no apparent side effects of this treatment including body weight loss or biochemical abnormalities in contrast to the treatment with AdCATK that conferred strong but nonspecific expression of the HSV-TK gene. These results suggested that AdMycTK/GCV therapy is effective on SCLC patients whose tumors overexpress myc family oncogenes.

Adenoviridae↗

PubMed2001

Clinicopathological study of carcinomas of the lip and the mucosa of the upper and lower lips.

BACKGROUND: Lip carcinomas are rare oral tumors, and there have been few reports of lip carcinoma in Japan. METHODS: Of 914 patients with oral carcinomas treated between January 1980 and December 1998, 12 (1.3%) had lip carcinoma and 5 (0.5%) had lip mucosal carcinoma. We investigated the clinicopathological features of these 17 patients. RESULTS: Of the 12 patients with carcinoma of the lip, 10 had squamous cell carcinomas (9, external lower lip; 1 commissures) and 2 had mucoepidermoid carcinomas (external upper lip). Of the 5 patients with lip mucosal carcinoma, 3 had squamous cell carcinomas (2, mucosa of the lower lip; 1, mucosa of the upper lip), 1 had mucoepidermoid carcinoma (mucosa of the lower lip), and 1 had acinic cell carcinoma (mucosa of the lower lip). Of the 12 patients with lip carcinoma, 9 were classified as stage I, 2 as stage II, and 1 as stage III; all 5 of the patients with lip mucosal carcinoma were stage I. Five patients with lip carcinoma were treated by resection, 5 by a combination of resection and reconstruction, and 2 by radiotherapy alone. All patients with lip mucosal carcinoma were treated by resection. After the initial therapy, 3 patients without neck dissection had regional recurrences and received delayed neck dissection, and 2 died with neck regional recurrence after dissection. The 5-year cumulative survival rates of the patients with lip carcinoma and those with lip mucosal carcinoma were 82.5% and 80.0%, respectively. CONCLUSION: We suggest that early-stage carcinomas of the lip and of the mucosa of the upper and lower lips are frequent, and we found that the outcome of these patients was excellent. However, an aggressive therapeutic approach to the lip carcinoma patient with cervical metastasis appears warranted, in an attempt to improve locoregional control and ultimate survival.

Aged↗

PubMed2001

Development status of Terumo implantable left ventricular assist system.

We have been developing an implantable left ventricular assist system (T-ILVAS) featuring a magnetically suspended centrifugal pump (MSCP) since 1995. In vitro and in vivo studies using a prototype MSCP composed of a polycarbonate housing and impeller (196 ml) have demonstrated long-term durability and excellent blood compatibility for up to 864 days, and excellent stability of the magnetic bearing of the MSCP. These preliminary results strongly suggested that the magnetic bearing of the MSCP is reliable and is a most feasible mechanism for a long-term circulatory assist device. We have recently devised a clinical version pump made of titanium (180 ml) with a new position sensor mechanism and a wearable controller with batteries. Cadaver fit study confirmed that the Type IV pump could be implanted in a small patient with a body surface area as small as 1.3. The in vitro performance tests of the Type IV pump demonstrated excellent hydrodynamic performances with an acceptable hemolysis rate. New position sensors for the titanium housing showed more uniform sensor outputs of a magnetic bearing than in the prototype polycarbonate pump. The Type IV pump then was evaluated in vivo in 6 sheep at the Oxford Heart Centre. Four sheep were electively sacrificed at 3 months and were allowed to survive for more than 6 months for long-term evaluation. In this particular series of experiments, no anticoagulant/antiplatelet regimen was utilized except for a bolus dose of heparin during surgery. There was a left ventricular mural thrombi around the inflow cannula in 1 sheep. Otherwise, there was no mechanical failure nor sign of thromboembolism throughout the study.

Animals↗

PubMed2001

Association of Epstein-Barr virus with tumor cell proliferation: clinical implication in nasopharyngeal carcinoma.

Nasopharyngeal carcinoma (NPC) is characterized by its association with Epstein-Barr virus (EBV) infection. Unlike other upper aerodigestive tract squamous cell carcinomas, clinical and pathologic features are unable to predict outcome in NPC. EBV has been demonstrated to have transforming potential in B-cell systems so that its infection can rapidly and efficiently induce sustained lymphocyte proliferation in vitro. However, the relationship between cell proliferation and EBV infection in NPC has not been previously reported. This study was designed to determine the association of EBV infection and NPC tumor cell proliferation. Cell proliferation index, as measured by two markers, PCNA and Ki-67, were moderately correlated (r=0.534, p=0.033). Quantitative analysis of EBV positivity was highly correlated with both cell proliferation indices (r=0.802, p=0.0039 and r=0.720, p=0.0174 for PCNA and Ki-67, respectively). TNM staging did not demonstrate prognostic significance. NPC patients whose tumors were EBV positive demonstrated increased survival compared with patients whose tumors were EBV negative (p=0.043). These results indicate that EBV infection may regulate cell proliferation in NPC and the presence of EBV can be used as a positive prognostic factor.

Adult↗

PubMed2000

Comparison of Emory and Cedars-Sinai methods for assessment of left ventricular function from gated myocardial perfusion SPECT in patients with a small heart.

To evaluate the effect of left ventricular (LV) size on the calculation of LV function from gated myocardial SPECT with Emory and Cedars-Sinai programs, we performed 99mTc-tetrofosmin gated SPECT on 49 patients with ischemic heart disease. End-diastolic volume (EDV), end-systolic volume (ESV), and ejection fraction (EF) were semi-automatically calculated by each program. All patients underwent left ventriculography (LVG) within 3 months before and after the SPECT study. We grouped the patients into 22 with a calculated ESV obtained from LVG of over 50 ml (group A) and 27 with an ESV value of 50 ml or below (group B). We then compared the ESV values from gated SPECT with those from LVG in each group. In group A, the ESV from both Emory and Cedars-Sinai programs similarly correlated well with those from LVG (r = 0.92 and r = 0.93, respectively), but in group B, the ESV calculated from the Cedars-Sinai program correlated less with those from LVG (r = 0.53) than those from the Emory program did (r = 0.70). The calculated LV volumes had more errors in the Cedars-Sinai program than in the Emory program, when a patient had a small heart.

Adult↗

PubMed2000

Simultaneous assessment of Tc-99m-sestamibi and I-123-BMIPP myocardial distribution in patients with myocardial infarction: evaluation of left ventricular function with ECG-gated myocardial SPECT.

123I-labeled 15-(p-iodophenyl)-3R,S-methyl pentadecanoic acid (BMIPP) is a branched-chain free fatty acid that is used to evaluate various cardiac diseases. The aim of the present study was to investigate the relationship between myocardial perfusion (99mTc-sestamibi) and BMIPP uptake, and to correlate perfusion and metabolic alterations with regional left ventricular dysfunction in patients with myocardial infarction (MI). ECG-gated dual-isotope myocardial SPECT was performed on 130 patients with MI with sestamibi (555 MBq) and BMIPP (148 MBq). The patients were classified into 3 groups according to PTCA therapy and the interval between the onset of infarction and RI injection (OR time). Group A (n = 56) included patients whose OR time was less than one month and who had undergone successful PTCA, Group B (n = 36) had OR times of less than one month and had conservative medical therapy, and Group C (n = 38) had OR times of over one month. The severity scores of the dual-isotope images were calculated from the defect scores in 9 segments. From the ECG-gated SPECT data with sestamibi, the left ventricular ejection fraction (LVEF; %) and regional wall motion were determined automatically using the QGS program LVEF obtained from gated SPECT correlated well with the severity scores for sestamibi and BMIPP (r = -0.68 and -0.76, respectively). The delta severity scores (BMIPP scores - sestamibi scores) of Group A were significantly higher than those of the other two groups (3.6 +/- 3.0 vs. 1.5 +/- 1.7 and 1.0 +/- 1.4, p < 0.001 ). The rate of dysfunctional segments with normal sestamihi distribution was significantly higher in Group A than in Group C (20.7% vs. 6.7%, p < 0.001). ECG-gated dual-isotope SPECT is useful since myocardial perfusion, fatty acid metabolism and left ventricular function can be analyzed during a single examination, so that this procedure has the potential to provide comprehensive information when evaluating patients with ischemic heart disease.

Adult↗

PubMed2000

Physical model-based indirect measurements of blood pressure and flow using a centrifugal pump.

This article describes a technique offering indirect measurements of pump pressure differential and flow with certain accuracy independent of changes in blood viscosity. This technique is based on noninvasive measurements of the motor current and rotation speed using the physical model equations of the centrifugal pump system. Blood viscosity included in the coefficients of the dynamic equations is first estimated, and then substitution of the estimated viscosity into the steady equations of the model provides pump flow and pressure differential. In vitro tests using a Capiox pump showed a sufficient linear correlation between actual values and their estimates for pressure differential and pump flow. An in vivo test using a 45 kg sheep showed that the proposed algorithm needs robustness for the convergence of estimates of viscosity. An overall evaluation, however, of the developed algorithm/model showed indications of success in terms of efficient computation and modeling.

Algorithms↗

PubMed2000

Intracranial lipomas: demonstration by computed tomography and magnetic resonance imaging.

We present two cases of a very rare tumor, intracranial lipoma, diagnosed by computed tomography (CT) and magnetic resonance imaging (MRI). In one case, the lipoma was in the superior cerebellar cistern, the other was in the periphery of the corpus callosum. In the case in which MRI was used, identification of the lipoma using a routine MRI examination was difficult. These cases are reported now because the incidental diagnosis of intracranial lipoma is likely to increase due to advanced neuroradiological techniques such as CT and MRI.

Brain Neoplasms↗

PubMed1999

Mesoporous Magnetic Materials Based on Rare Earth Oxides.

A novel family of mesoporous oxides of rare earth metals (Gd, Tb, Dy, Ho, Er, Tm, Yb, Lu) were synthesized with specific surface areas of 253-348 m(2) g(-1) and pore diameters of 2.5-3.0 nm (see Scheme). The mesoporous solids and their surfactant mesophase precursors are paramagnetic and exhibit a magnetic anomaly due to the mesostructured atomic arrangement.

Journal Article↗

PubMed1999

Application of the Cre recombinase/loxP system further enhances antitumor effects in cell type-specific gene therapy against carcinoembryonic antigen-producing cancer.

A considerable number of studies of cancer have shown that the cell type-specific promoter is an effective tool for selective expression of foreign genes in tumor cells. However, few reports have demonstrated significant in vivo antitumor effects using this strategy thus far, possibly because the low activity of such a promoter results in insufficient expression of genes in cancer cells as well as in insignificant antitumor effects, even when the cells are infected by highly efficient gene transfer methods. To overcome this problem, we used the Cre/loxP system for the cell type-specific gene therapy against carcinoembryonic antigen (CEA)-producing cancer. We constructed a pair of recombinant Ads. One expresses the Cre recombinase (Cre) gene under the control of the CEA promoter (Ad.CEA-Cre). The other contains the herpes simplex virus thymidine kinase (HSV-TK) gene separated from the strong CAG promoter by insertion of the neomycin resistance (neo) gene (Ad.lox-TK). The HSV-TK gene of the latter Ad is designed to be activated through excisional deletion of the neo gene by Cre enzyme released from the former one only when CEA-producing cells are infected simultaneously with these Ads. Coinfection by these Ads rendered a human CEA-producing cancer cell line 8.4-fold more sensitive to ganciclovir (GCV) compared with infection by Ad.CEA-TK alone, the HSV-TK gene of which is directly regulated by the CEA promoter. On the other hand, coinfection with these Ads did not significantly change the GCV sensitivity of non-CEA-producing cells. Intratumoral injection of Ad.CEA-Cre combined with Ad.lox-TK followed by GCV treatment almost completely eradicated CEA-producing tumors established in the subcutis of athymic mice, whereas intratumoral injection of Ad.CEA-TK with GCV administration at most retarded the growth of inoculated tumors. These results suggest distinct advantages of the Cre/loxP system applied in the conventional cell type-specific gene therapy against cancer.

Adenocarcinoma↗

PubMed1999

Measurement of blood hematocrit inside the magnetically suspended centrifugal pump using an optical technique: application to assessment of pump flow.

To measure blood hematocrit inside the magnetically suspended centrifugal pump, we have performed both forward and backward light scattering measurements using a specially designed optical cell. In the forward scattering measurement, an optical fiber was used to guide the near infrared light at 780 nm into a 250 microns gap region, and the light that forward scattered toward a detector fiber was measured using a phototransistor. The light intensity decreased exponentially with an increase in the hematocrit to around 20%. The forward scattering method suffered from sensitivity at the hematocrit levels around 25-45% due to the diffusion effect. By making the optical path length larger than several millimeters, the sensitivity of the forward scattering method in terms of hematocrit change can be improved. In the back scattering method, however, better sensitivity in terms of hematocrit change from 0-50% was obtained. By making the optical fiber separation distance less than 1 mm, the system will measure the first order back scattering from the shallow layer while, by making the fiber separation distance larger than several millimeters, the system will primarily measure the diffuse reflectance from the deeper layer. Both approaches will yield sensitive optical intensity change in terms of the physiological hematocrit range.

Algorithms↗

PubMed1999

Left ventricular function at rest and during bicycle exercise in normal subjects: assessment by ECG-gated myocardial perfusion SPET with 99Tcm-tetrofosmin.

99Tcm-labelled myocardial perfusion tracers allow simultaneous assessment of myocardial perfusion and left ventricular function using ECG-gated SPET. The aim of this study was to evaluate left ventricular performance during exercise by means of ECG-gated myocardial perfusion SPET. After the administration of 99Tcm-tetrofosmin (555-740 MBq), eight healthy volunteers aged 27-49 years underwent ECG-gated myocardial perfusion SPET at rest and during supine submaximal exercise (75 and 125 W), for 3 min each. Using ECG-gated SPET data, left ventricular end-diastolic volume (LVEDV) demonstrated a biphasic response during exercise (from 106.4 +/- 17.5 to 119.9 +/- 19.9 to 108.1 +/- 19.2 ml). In contrast, left ventricular end-systolic volume decreased gradually and significantly during exercise (from 47.1 +/- 11.9 to 41.5 +/- 8.9 to 36.1 +/- 10.1 ml; P < 0.05), and left ventricular ejection fraction continued to increase at higher workloads (from 56.1 +/- 6.0 to 63.0 +/- 2.7 to 67.0 +/- 4.3; P < 0.01) despite a fall in LVEDV. There was a progressive increase in cardiac output during exercise, which reached a peak of 7.2 +/- 0.9 l.min-1. We conclude that ECG-gated myocardial perfusion SPET can assess left ventricular function during exercise and may provide useful information for the evaluation of patients with ischaemic heart disease.

Adult↗

PubMed1999

[Myocardial distribution of iodine-123-iodophenyl-9-methyl-pentadecanoic acid (9MPA) in patients with acute myocardial infarction: comparison with regional wall motion obtained from technetium-99m-sestamibi gated SPECT].

123I-iodophenyl-9-methyl-pentadecanoic acid (9MPA) is a modified long-chain (15 carbons) fatty acid with a methyl branch on its 9 carbon location. Myocardial SPECT images (two sets, 10 min each) were obtained starting 10 min (early phase) and 50 min (delay phase) after the injection of 160 MBq 123I-9MPA at rest in 10 patients with acute myocardial infarction. The segmental myocardial uptake (% uptake) and clearance (% washout) from early to delay image were calculated by the SPECT data. ECG-gated myocardial SPECT with 99mTc-sestamibi was also performed and segmental left ventricular (LV) wall motion was evaluated using QGS (quantitative gated SPECT) program. The % uptake of LV segments with hypokinetic or akinetic wall motion were significantly lower than those with normokinesis (p < 0.01) for both early and delay phases. The % washout of hypokinetic segments were significantly lower than those of normokinetic regions (p < 0.01), while the % washout of akinetic segments were significantly higher than those of severely hypokinetic segments (p < 0.05). Thus, 123I-9MPA myocardial distribution and clearance thought to be associated with left ventricular regional wall motion.

Fatty Acids↗

PubMed1999

[Accuracy of intraocular power calculation formulas].

PURPOSE: We examined the accuracy of intraocular lens power calculation formulas, with special emphasis on the prediction of refraction in different axial lengths. MATERIAL AND METHODS: 786 cases were subdivided into four groups based on the axial length (short axial length < 22.0 mm, normal axial length = 22-24.4 mm, mid-range axial length = 24.5-26.9 mm and long axial length > 27 mm). Seven different formulas (Holladay, SRK, SRK II, SRK/T, S-SRK, M-SRK, L-SRK) were tested for their accuracy in predicting post-operative refraction. RESULT: The best results were obtained using the S-SRK formula in the short axial length group (n = 114), The SRK and Holladay formulas in the normal axial length group (n = 278). The Holladay and SRK/T formulas in the mid-range axial length group (n = 135), and the SRK/T and L-SRK in the long axial length group (n = 259). CONCLUSION: Our results emphasize the importance of using an intraocular lens formula specific for each range of axial length when calculating the predicted refraction.

Aged↗

PubMed1999

[Assessment of left ventricular contraction abnormalities with myocardial infarction using gated technetium-99m sestamibi SPECT: comparison of wall thickening and regional ejection fraction analysis for the detection of coronary artery stenosis].

ECG-gated myocardial Technetium-99m sestamibi SPECT is a useful technique to measure myocardial perfusion and function simultaneously. In this study, wall thickening (WT) and regional ejection fraction (rEF) using ECG-gated SPECT have been studied to determine which parameter would be more sensitive to detect coronary artery stenosis in patients with acute myocardial infarction (AMI). Forty-five patients (36 men, 9 women, mean age 63 +/- 9 years old) with AMI were examined. CAG was performed for all patients. ECG-gated SPECT was performed 60 min after the intravenous injection of 555 MBq 99mTc-sestamibi at rest. Commercially available software (QGS) was used to produce WT and rEF polar maps from acquired SPECT data. The WT and rEF polar maps were evaluated visually and quantitatively. WT indicated higher sensitivity (80.3% vs. 59.1%, p < 0.05) and accuracy (86.7% vs. 74.8%, p < 0.05) than rEF for detecting overall coronary artery stenosis on visual interpretation. On quantitative analysis, WT had higher specificity (91.3% vs. 75.4%, p < 0.05) and accuracy (85.9% vs. 72.6%, p < 0.05) than rEF for detecting overall coronary artery stenosis, and showed a higher specificity (93.8% vs. 59.4%, p < 0.01) and accuracy (88.9% vs. 62.2%, p < 0.01) for detecting LCX stenosis. Moreover, sensitivity of WT for detecting coronary artery stenosis without infarction was higher than that of rEF significantly in quantitative analysis (75.0% vs. 31.3%, p < 0.05). These results suggested that WT was superior to rEF for detecting the coronary artery stenosis in patients with and without myocardial infarction. We concluded that WT is more sensitive indicator to determine localization of regional left ventricular dysfunction in AMI than rEF.

Aged↗

PubMed1998

Rapid data acquisition protocol in ECG-gated myocardial perfusion SPECT with Tc-99m-tetrofosmin.

Into 25 patients with heart disorders, 99mTc-tetrofosmin 555-740 MBq was injected intravenously at rest. After 40 minutes, ECG-gated myocardial perfusion SPECT was performed with a two detector gamma camera VERTEX (ADAC), setting up two detectors to form a 90-degree angle. Sixteen frames per R-R interval were acquired during a 180 degree rotation from the RAO 45 degrees to the LPO 45 degrees. A pair of data sets with standard (SDA) and rapid data acquisition (RDA) protocols was collected. In an SDA protocol, SPECT imaging was performed for 50 sec per step in 5 degree angular steps (total acquisition time; 15 minutes). An RDA protocol was conducted with 12 sec per step, 6 degree angular steps (acquisition time, 3 minutes). LVEF (%) and LVEDV (ml) quantitated automatically with a QGS program showed excellent correlations between two protocols with correlation coefficients of 0.980 (p < 0.01) and 0.983 (p < 0.01), respectively. Subsequently visual assessment of regional wall motion based on a four-point grading system was carried out with a 3-D cine LV display. High complete agreement was gained with 158 (90.3%) out of total 175 segments, so that assessment of the global and regional LV function with the RDA protocol demonstrated high reliability and feasibility.

Electrocardiography↗

PubMed1998

Cloning and tissue expression of cDNAs from chromosome 5q21-22 which is frequently deleted in advanced lung cancer.

Previously, we have reported that the inactivation of putative tumor-suppressor gene(s) on chromosome 5q21-22 may play an important role in the progression of lung cancer. Here, we describe the establishment of a yeast artificial chromosome (YAC) contig that spans 8-10 Mb at the 5q21-22 region. Six cosmid contigs have also been established in this YAC contig. About 35 exon-like fragments have been detected by exon-amplification, direct screening, cross-species hybridization, and searches of a database. Thus far, 14 cDNAs have been isolated, and two of them coincide with known genes, viz., cysteine dioxygenase I and geranylgeranyltransferase I. The other 12 cDNAs are considered to be novel genes. Two of these novel cDNA show partial homology to known genes, viz., semaphorin CD100 and the 28S rRNA gene. In addition, four known genes, including APC (adenomatous polyposis coli), MCC (mutated in colorectal cancer), proto-oncogene tyrosine kinase FER, and genomic imprinted gene U2AF1-RS1, have also been mapped in this contig. This large contig and expression map should prove crucial in the identification of susceptibility gene(s) related to the progression of lung cancer.

Chromosome Deletion↗