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Biomedical subjects

S D Yeh

Publications and source records attributed to S D Yeh.

At least 37 records · Page 2Linked to original sources

Survival from locally invasive or widespread neuroblastoma without cytotoxic therapy.

PURPOSE: To test the hypothesis that cytotoxic therapy is not needed at diagnosis to assure the survival of most patients with non-stage 4 neuroblastoma. METHODS: Patients with non-stage 4 disease received no cytotoxic therapy in the absence of N-myc amplification. The International Neuroblastoma Staging System (INSS) was used. RESULTS: Of 84 consecutive patients with previously untreated, newly diagnosed neuroblastoma, 31 (37%) had non-stage 4 disease. All 31 patients initially received no cytotoxic therapy because none of them had N-myc amplification. Nine stage 1 patients are relapse-free. This report focuses on the 22 patients with locally invasive or distant disease: two stage 2A with gross residual tumor postsurgery, 11 stage 2B with ipsilateral or midline lymph node involvement, four stage 3, and five stage 4S. Eight of the 22 patients were older than 1 year. Postsurgery, 13 patients had visible residual disease, and two others had markedly increased urinary catecholamine levels for more than 1 year. Recurrent or enlarging tumors regressed spontaneously (n = 2) or were excised 5 to 39 months after diagnosis (n = 4). One of the latter had chromosome 1p deletions (common in poor-risk neuroblastoma) that were not detected in the patient's original tumor resected 23 months earlier--findings consistent with clonal evolution or multifocal disease. The patient received chemotherapy. All 22 patients are alive 24 to 98 months (median, 64) from diagnosis. CONCLUSION: Our results suggest that non-stage 4 patients without N-myc amplification can be spared cytotoxic therapy because (1) residual postsurgical or recurrent biologically favorable neuroblastoma rarely evolves into lethal stage 4 disease; and (2) neuroblastoma in lymph nodes has no prognostic significance. These findings are remarkable because no other cancer includes subtypes that are curable without therapy to ablate residual disease.

Adolescent↗

Quantitative studies of monoclonal antibody targeting to disialoganglioside GD2 in human brain tumors.

Iodine-131 3F8, a murine IgG3 monoclonal antibody that targets to GD2-bearing tumors, was administered intravenously to 12 patients with brain tumors. Six patients received 2 mCi (0.74 Bq) of 131I-3F8, five patients 10 mCi (3.7 Bq)/1.73 m2 of 131I-3F8, and one patient 2.6 mCi (0.96 Bq) of 124I-3F8, with no side-effects. Nine of 11 malignant gliomas and the single metastatic melanoma showed antibody localization, with the best tumor delineation on single-photon emission tomography (SPET) following 10 mCi (3.7 Bq)/1.73 m2 dose. No nonspecific uptake in the normal craniospinal axis was detected. There was no difference in the pharmacokinetics of low-dose versus the higher-dose antibody groups; plasma and total-body half-lives were 18 h and 49 h, respectively. Surgical sampling and time-activity curves based on quantitative imaging showed peak uptake in high-grade glioma at 39 h, with a half-life of 62 h. Tumor uptake at time of surgery averaged 3.5 x 10(-3) %ID/g and peak activity by the conjugate view method averaged 9.2 x 10(-3) %ID/g (3.5-17.8). Mean radiation absorption dose was 3.9 rad per mCi injected (range 0.7-9.6) or 10.5 cGy/Bq (range 1.9-26). There was agreement on positive sites when immunoscintigraphy was compared with technetium-99m glucoheptonate/diethylene triamine penta-acetic acid planar imaging, thallium-201 SPET, and fluorine-18 fluorodeoxyglucose positron emission tomography. Taken together, these data suggest that quantitative estimates of antibody targeting to intracranial tumors can be made using the modified conjugate view method.

Adolescent↗

Image registration of SPECT and CT images using an external fiduciary band and three-dimensional surface fitting in metastatic thyroid cancer.

Image registration of 131I SPECT with CT scans was performed in a patient with metastatic thyroid carcinoma using an external fiduciary band and a three-dimensional surface-fitting algorithim. Areas of metastatic disease taking up 131I were accurately localized to the liver, lungs and vertebral bodies; providing information that could not be obtained by planar or SPECT images alone. Based on these findings, further invasive diagnostic procedures were not performed, therefore considerably altering management in this patient. This approach to image registration has immediate clinical utility in the registration and interpretation of SPECT studies with corresponding CT or MRI scans.

Algorithms↗

The value of thallium and three-phase bone scans in the evaluation of bone and soft tissue sarcomas.

Thirty-seven patients with newly diagnosed or treated sarcomas had 47 sets of sequential thallium scans (TS) followed by three-phase bone scan (TPBS) on the same day. The diagnosis in all patients was verified by biopsy (n = 40) or long-term follow-up studies (n = 7). The sensitivity, specificity, and accuracy of TS and TPBS in detecting sarcomatous lesions was calculated: TS sensitivity was 88%, specificity 69%, and accuracy 83%; blood flow (BF) and blood pool (BP) sensitivity was 91%, specificity 54%, and accuracy 81%; delayed bone scan (DB) sensitivity was 88%, specificity 38%, and accuracy 74%. In 17 studies the flow and blood pool parts of the TPBS and TS demonstrated the soft tissue component of sarcomas, which would have been missed if only the delayed bone scan had been performed. The TS lesion to normal tissue ratio alone was not very helpful in differentiating sarcomas from benign conditions because some benign lesions are highly cellular and vascular while some malignant lesions, such as chondrosarcoma, have poor vascularity and a less cellular chondroid matrix. However, when the thallium ratio was correlated with similar ratios calculated from the BP image, it was found that if the TS lesion to normal tissue ratio exceeded the BP lesion to normal tissue ratio (12 patients), the specificity for detecting sarcomatous lesions was 100%. Nevertheless, the reverse was not true. The positive predictive value of this observation was 100% and the negative predictive value was 37%.

Adolescent↗

Nucleotide sequence of the coat protein coding region of the potyvirus tobacco vein-banding mosaic virus.

The sequence of the 3' 1184 nucleotides of tobacco vein-banding mosaic virus (TVBMV) genome has been determined. It contains a single open reading frame which encompasses the whole of the coat protein of TVBMV. The sequence of the first 20 amino acids at the N-terminal region of the coat protein has also been determined chemically to be GDDQTVDAGKNVQSNQKQRN. The sequence matches the translation product of the open reading frame starting with amino acid-271; a glycine residue. Thus the coat protein of TVBMV has a calculated M(r) of 30,210. The 3' non-coding region of TVBMV is 185 nucleotides in length. Sequence alignment of the coat proteins or the 3' non-coding regions from TVBMV and other reported potyviruses indicated that TVBMV is a separate species of the potyvirus genus.

Amino Acid Sequence↗

Gallium-67-citrate imaging in nuclear oncology.

Gallium-67-citrate is one of the most useful radiopharmaceuticals to detect tumors, stage extent of the disease, monitor response to treatment and distinguish recurrent disease from post-treatment changes. Gallium is likewise very sensitive to detect and locate infections and inflammatory foci. This application is extremely important in the management of immunocompromised cancer patients. Image interpretation should be tempered with full knowledge of the patients clinical condition, anatomic alterations due to prior surgery and correct timing of image acquisition. Early imaging at 4-6 h is useful to detect gastrointestinal infections, whereas 24 h imaging is used to evaluate chest infections. Although gallium-67 is a non-specific agent, the identification of the etiology of the inflammation may be improved by adequate clinical and laboratory information as well as correlation with other imaging modalities such as sonography and computerized x-ray tomography (CT). High dose (10 mCi) gallium-67 single photon emission computed tomography (SPECT) imaging with image co-registration is important for accurate uptake localization.

Citrates↗

Development of a method to measure kinetics of radiolabelled monoclonal antibody in human tumour with applications to microdosimetry: positron emission tomography studies of iodine-124 labelled 3F8 monoclonal antibody in glioma.

We present a method to assess quantitatively the immunological characteristics of tumours using radiolabelled monoclonal antibody and positron emission tomography (PET) to improve dosimetry for radioimmunotherapy. This method is illustrated with a glioma patient who was injected with 96.2 MBq of iodine-124 labelled 3F8, a murine antibody (IgG3) specific against the ganglioside GD2. Serial PET scans and plasma samples were taken over 11 days. A three-compartment model was used to estimate the plasma to tumour transfer constant (K1), the tumour to plasma transfer constant k2, the association and dissociation constants (k3, k4) of antibody binding, and the binding potential. Tumour radioactivity peaked at 18 h at 0.0045% ID/g. The kinetic parameters were estimated to be: K1 = 0.048 ml h-1 g-1, k2 = 0.16 h-1, k3 = 0.03 h-1, k4 = 0.015 h-1 and BP = 2.25. Based on these kinetic parameters, the amount of tumour-bound radiolabelled monoclonal antibody was calculated. This method permits estimates of both macrodosimetry and microdosimetry at the cellular level based on in vivo non-invasive measurement.

Brain↗

Serological comparison of tospovirus isolates from Taiwan and India with impatiens necrotic spot virus and different tomato spotted wilt virus isolates.

Tospovirus isolates from tomato and watermelon in Taiwan and from peanut in India reacted neither with antibodies to tomato spotted wilt virus (TSWV), nor with antibodies to impatiens necrotic spot virus (INSV), in ELISA and in electroblot immunoassays. Additionally, all three tospovirus isolates had an N protein with a molecular weight of 32 kDa as compared to 29 kDa for the N protein to TSWV and INSV. The observed physicochemical and serological differences suggest the generation of a new, third species in the genus tospovirus for which we propose the name groundnut bud necrosis virus.

Antigens, Viral↗

Nucleotide sequence comparison of the 3'-terminal regions of severe, mild, and non-papaya infecting strains of papaya ringspot virus.

The 3'-terminal 2,561 nucleotide residues of the severe HA strain of papaya ringspot virus (PRSV) was determined. Comparison with the published sequence of the mild strain PRSV HA 5-1 showed that they shared a 99.4% identity in their 3'-terminal 2,235 residues. There were ten residues different at the NIb gene, resulting in five amino acid changes, and two residues different in the coat protein gene, resulting in two amino acid changes. The 3'-untranslated regions were identical, but HA contained two more nucleotides (AG) at the 3' extreme. Comparison with the published non-papaya infecting type W strain PRSV-W revealed that they shared a 97.9% identity in their 3'-terminal 2,235 residues. There were 40 nucleotides different in the coding region, which resulted in four amino acid changes in the NIb gene and six in the CP gene, and seven nucleotides different in the 3'-untranslated region.

Amino Acid Sequence↗

Genitourinary tract nuclear oncology.

Currently available routine radionuclide procedures and on-going investigational scintigraphic studies of genitourinary tract tumors were reviewed. Emphasis was focused on the most commonly encountered tumors located in the kidneys, bladder, and prostate. Other imaging modalities, such as computed tomography (CT), magnetic resonance imaging (MRI), and sonography have replaced many of the routine radionuclide imaging procedures providing high-resolution images and anatomic details. The advantages of radionuclide procedures with their simple, uninvasive, and functioning nature will continue play important role in our management of tumors of the genitourinary tract.

Female↗

The relationship between thallium uptake, blood flow, and blood pool activity in bone and soft tissue tumors.

Twenty patients with known primary untreated and recurrent bone and soft tissue tumors underwent thallium imaging and three-phase bone imaging in the same session. The ratio of thallium uptake in the tumor tissue to the contralateral normal tissue areas was compared with the same ratio for phase 1 (blood flow or arterial phase), phase 2 (blood pool), and phase 3 (delayed medroxy-diphosphonate, MDP, uptake). There was poor correlation between Tl uptake and phases 1 and 3 of the bone scan ratios; r = 0.37 and 0.46; P = 0.097 and 0.047, respectively. The thallium uptake ratios correlated well with blood pool ratios (phase 2) (r = 0.84 and P less than 0.01). In contrast to uptake into normal muscle, Tl-201 uptake into tumor is not highly dependent on blood flow alone and other factors predominate in determining its magnitude.

Bone Neoplasms↗

Complete nucleotide sequence and genetic organization of papaya ringspot virus RNA.

The complete nucleotide sequence of the RNA genome of papaya ringspot virus (PRSV) was determined from four overlapping cDNA clones and by direct sequencing of viral RNA. The genomic RNA is 10326 nucleotides in length, excluding the poly(A) tract, and contains one large open reading frame that starts at nucleotide positions 86 to 88 and ends at positions 10118 to 10120, encoding a polyprotein of 3344 amino acids. The highly conserved sequence AAAUAAAANANCUCAACACAACAUA at the 5' end of the RNA of PRSV and those of the other five reported potyviruses shows 80% similarity, suggesting that this region may play a common important role for potyvirus replication. Two cleavage sites of the polyprotein were determined by amino acid sequencing of the N termini of helper component (HC-Pro, amorphous inclusion) and cylindrical inclusion (CI) proteins. Other cleavage sites were predicted by analogy with the other potyviruses. The genetic organization of PRSV is similar to that of the other potyviruses except that the first protein processed from the N terminus of the polyprotein (NT protein) has an M(r) of 63K, 18K to 34K larger than those of the other potyviruses. The cleavage site for liberating the N terminus of the HC-Pro protein was found at the same location down-stream from the consensus sequence FI(V)VRG as that reported for tobacco vein mottling virus. The NT protein of potyviruses is the most variable and may be considered important for identification of individual potyviruses. The most conserved protein of potyviruses appears to be the NIb protein, the putative polymerase for the replication of the potyviral RNA. The genetic organization of PRSV RNA is tentatively proposed to be VPg-5' leader-63K NT-52K HC-Pro-46K-72K CI-6K-48K NIa-59K NIb-35K coat protein-3' non-coding region-poly(A) tract.

Amino Acid Sequence↗

Validation of gallium-67-citrate single-photon emission computed tomography in biopsy-confirmed residual Hodgkin's disease in the mediastinum.

In a retrospective study of a series of 30 adult patients during restaging of Hodgkin's disease after therapy, computed tomography (CT) and biopsy results were correlated with 67Ga SPECT in order to determine the value of SPECT imaging in monitoring recurrent mediastinal Hodgkin's disease. SPECT had an overall accuracy of 93% (28/30) and correctly identified active disease in 24 of 25, 96% of histopathologically proven recurrent Hodgkin's disease. Thus in this post-therapy setting, we have confirmed the high sensitivity of 67GA SPECT scans in patients selected for biopsy. Gallium-67 may prove particularly useful in detecting residual disease activity in patients in whom biopsy was positive but the interpretations of the CT scans were uncertain in regard to presence of tumors [8/30 (27%)]. In this group of patients, we found SPECT particularly helpful. A larger prospective series is under way to assess this possibility.

Adult↗

Phase I and imaging trial of indium 111-labeled anti-epidermal growth factor receptor monoclonal antibody 225 in patients with squamous cell lung carcinoma.

Murine monoclonal antibody (MAb) 225 (IgG1) against the epidermal growth factor (EGF) receptor competitively blocks EGF binding and inhibits EGF-induced activation of receptor tyrosine kinase and cell proliferation. The effect of MAb 225 was studied in a phase I trial in patients with inoperable squamous cell carcinoma of the lung, which invariably expresses high levels of EGF receptors. Groups of three patients received total doses of MAb 225 ranging from 1 mg to 300 mg. Except at the lowest dose, each infusion included 4 mg of indium 111 (111In)-labeled MAb 225. No toxicity was observed. Tumors were imaged in all patients who received doses of 20 mg or greater. Presumed metastases greater than or equal to 1 cm in diameter were imaged with doses of 40 mg or greater. Single-photon-emission-computed tomography could be carried out at the 120-mg and 300-mg doses and significantly improved tumor visualization. All patients produced anti-murine antibodies. We conclude that treatment with an MAb that inhibits EGF receptor function is safe at the doses and schedule studied. 111In-labeled MAb images squamous cell lung carcinoma; tumor uptake of the labeled MAb is dose dependent. Further studies are warranted to explore the potential therapeutic efficacy of anti-EGF receptor MAbs and other agents that act in a comparable manner.

Adult↗