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Biomedical subjects

W D Kaplan

Publications and source records attributed to W D Kaplan.

At least 19 recordsLinked to original sources
PubMed2001

Prognostic significance of the number of bone scan abnormalities at the time of initial bone metastatic recurrence in breast carcinoma.

BACKGROUND: To gain insight into the factors that contribute to the more favorable prognosis associated with recurrence limited to bone in patients with breast carcinoma, the authors analyzed the number of sites of initial involvement identified on radionuclide bone scans in relation to long term outcome. METHODS: Records of 641 patients with clinical Stage I-III breast carcinoma that originally was diagnosed in 1974-1985 were reviewed. During follow-up, 295 patients (46%) experienced distant recurrence, including 116 with bone as the sole initial site of metastatic disease. Radionuclide bone scans identified the initial site(s) of recurrence in 113 of these latter 116 patients, and these studies were categorized by the number of skeletal lesions subsequently confirmed as metastases (1, 2, or > or = 3). Survival from time of recurrence and time of original diagnosis was analyzed using Kaplan-Meier methods, and factors associated with recurrence and mortality were examined using logistic and Cox regression. RESULTS: Median survival from time of recurrence was 35 months in the patients with bone-only metastases, compared with 11-26 months for all other sites of visceral recurrence exclusive of bone. Number of positive lymph nodes and estrogen receptor status were the only predictive variables for recurrence. Median survival from time of recurrence and time of original diagnosis for the 3 bone scan categories was: 1 lesion (n = 47), 53 and 86 months; 2 lesions (n = 22), 38 and 68 months; and > or = 3 lesions (n = 44), 22 and 58 months (P < 0.0001 and P < 0.005 for 1 and 2 lesions vs. > or = 3). In the "bone-only" group, the number of scan lesions was the strongest predictor of length of survival. CONCLUSIONS: Patients with breast carcinoma who experience a recurrence in bone at only one or two sites initially have a survival advantage over those with more extensive (> or = 3 sites) skeletal metastases and those with metastatic disease involving other visceral organs.

Adult↗
PubMed1997

An investigation of lymphatic function following free-tissue transfer.

Despite microsurgical advances in the repair of severed arteries, veins, and nerves, disrupted lymphatics are not usually identified or reconnected during replantation. Although temporary swelling of a replanted part is attributed to lymphedema, this condition resolves without microsurgical intervention. Spontaneous regeneration or reconnection of lymphatics is thought to occur in such situations. Microsurgical free-flap transfer is clinically analogous to replantation in that it also results in a complete division of all lymphatic channels exiting the flap. The ability of lymphatics to regenerate after flap reconstruction, either pedicled or free, has received little attention because safe and accurate techniques for visualization and evaluation of the status of these structures have not been available. As a result of recent advances in radiocolloid lymphoscintigraphic imaging techniques, it is possible to demonstrate lymphatic flow in a physiologic, anatomic, and noninvasive manner. These methods can be applied to free-flap models to document lymphatic function after surgical treatment and determine when and to what extent such a process of growth occurs. We studied 10 consecutive patients having free-flap reconstruction. These flaps were performed for chronic osteomyelitis (6) and unstable wound coverage (4). Microvascular flaps used were latissimus dorsi, scapular-parascapular fasciocutaneous, lateral arm, rectus abdominis, temporoparietal, and free toe. Radiocolloid lymphoscintigraphy with technetium-99m-antimony trisulfide colloid (Sb2S3) was done on all patients by injection directly into the free-flap dermis. All patients were studied between 8 and 44 days (mean 23.6) after free-flap transfer. Following injection into each flap, rapid egress of the radiotracer along lymphatic pathways with progression to locoregional nodes was observed in all patients. Reestablishment of lymphatic pathways following microvascular free-tissue transfer was demonstrated by radionuclide lymphoscintigraphic techniques in 10 consecutive patients who had reconstruction for extremity wounds.

Adolescent↗
PubMed1996

Bone lymphoma. Comparison of Tl-201 and Ga-67 citrate scintigraphy in assessment of treatment response.

Assessment of response to therapy in patients with lymphoma involving bone can be difficult. Of the scintigraphic techniques available, Tl-201 may be the most ideal radiopharmaceutical because it reflects tumor burden more accurately than either Tc-99m MDP or Ga-67 citrate. We compared serial Tl-201 and Ga-67 citrate scintigraphs (24 studies, 12 pairs) in assessing the response to therapy in three patients with non-Hodgkin's lymphoma involving bone. In two patients who demonstrated a complete remission, uptake of Tl-201 diminished more rapidly and returned to normal earlier than did Ga-67 citrate. Tl-201 did not show tumor recurrence in the one patient with lesions shown to be Tl-201 negative at baseline. Serial studies using Tl-201 may be superior to Ga-67 citrate in the evaluation of lymphoma involving bone provided that Tl-201 avidity is demonstrated on baseline studies.

Adult↗
PubMed1995

Protection against daunorubicin cytotoxicity by expression of a cloned human carbonyl reductase cDNA in K562 leukemia cells.

Carbonyl reductase (CBR) catalyzes the reduction of daunorubicin (DN) to its corresponding alcohol, daunorubicinol (DNOL), and changes the pharmacological properties of this cancer chemotherapeutic drug. The DN reductase associated with CBR reduces the C13 methyl ketone group and does not metabolize the quinone ring of DN. Reports comparing DN and DNOL toxicity have resulted in various conclusions depending on the cells tested. Differences in toxicity could be due to variations in several enzymes involved in DN metabolism. In this report, the effects of CBR expression on DN metabolism and cell toxicity were determined by cloning and expressing a human CBR cDNA in DN reductase-deficient myeloid erythroleukemia K562 cells. CBR activity increased 83-fold in the K562-transfected cells and was associated with a 2-3-fold reduction in DN toxicity. Maximum protection occurred at 30 nM DN where 94% of the intracellular DN was converted to DNOL within 2 h. The reduced toxicity was specific for DN. Other CBR substrates such as menadione, phenanthrenequinone, and doxorubicin were equally toxic to both the CBR expresser cells and the control cells under the conditions tested. Our results suggest that high levels of CBR in tumor cells could contribute to drug resistance. The results also suggest that reduction of DN to DNOL protects against DN toxicity by altering interaction of the drug at one or more of the many target sites.

Alcohol Oxidoreductases↗
PubMed1995

Cloning and expression of the cDNA encoding rabbit liver carbonyl reductase.

Two cDNA sequences encoding rabbit carbonyl reductase (CBR) were cloned from a lambda gt10 rabbit liver cDNA library. The rabbit cDNAs coded for a protein with 84% identity to human CBR. Transient expression of the two rabbit cDNA sequences in COS7 cells increased both quinone reductase and aldo-keto reductase activities. These data demonstrate that CBR cDNAs from rabbit and human tissues code for similar proteins.

Alcohol Oxidoreductases↗
PubMed1994

Changes in Tc-99m radionuclide bone scan images and peripheralization of marrow hematopoietic activity associated with the administration of granulocyte colony stimulating factor as an adjunct to dose-intensified chemotherapy for breast cancer. A case report.

Granulocyte colony stimulating factor (G-CSF) is used clinically for chemotherapy-associated neutropenia. Very little is known about the manner in which pharmacologic dosing of G-CSF may affect radiologic studies in vivo. Dramatic changes on bone scan associated with the administration of G-CSF used to support dose-intensified combination chemotherapy in a patient with metastatic breast carcinoma are described. The scintigraphic findings were correlated histologically with increased hematopoietic activity in the bone marrow located in peripheral bones.

Adult↗
PubMed1994

Healing flare in skeletal metastases from breast cancer.

PURPOSE: To identify the frequency, characteristics, and prognostic significance of scintigraphically detected healing flare in patients with breast cancer metastatic to bone. MATERIALS AND METHODS: Findings on bone scans and concomitant radiographs of 1,188 patients were reviewed. Bone metastases occurred in 426 patients. Outcomes of 101 patients (aged 21-71 years) with skeletal metastases were correlated with typical scintigraphic and radiographic features. RESULTS: Healing flare with increased radiotracer uptake and radiographically demonstrated sclerotic changes in osteolytic or mixed skeletal metastases were prospectively identified in 12% of patients with skeletal metastases. Healing flare was detected 3.2 months +/- 1.4 after initiation of hormonal treatment or chemotherapy. Skeletal metastatic activity stabilized on bone scans within 6.2 months +/- 3.0. Patients with healing flare did not survive longer than patients without healing flare but with stable metastases after treatment (3.3 years +/- 2.0 vs 3.9 years +/- 1.6). CONCLUSION: Scintigraphically detected healing flare represents a favorable response to therapy not associated with increased survival.

Adult↗
PubMed1994

Gallium-67-citrate imaging in extragonadal and gonadal seminomas: relationship to radiologic findings.

METHODS: The results and analysis of baseline and follow-up 67Ga imaging in three patients with extragonadal seminoma were compared to those of nine patients with primary and metastatic gonadal seminomas. Gallium-67 tumor avidity was scored (0-6) relative to accumulation in the sternum and the liver. Response time to systemic therapy for 67Ga imaging compared to other radiological examinations was also measured. RESULTS: Prior to therapy, 67Ga scan sensitivity was 100%, (3/3) in patients with extragonadal seminomas and 90%, (9/10) for primary and radiologically evident metastatic sites in patients with gonadal seminomas. The combined sensitivity was 92%, (12/13) with the smallest 67Ga scan detecting a mass 1.5 cm in diameter. There was no significant difference in 67Ga avidity or sensitivity between extragonadal and gonadal sites. Following chemotherapy, CT scanning demonstrated residual radiologic abnormalities in all three extragonadal seminoma tumor sites and 5/8 metastatic gonadal seminoma tumor sites. However, the 67Ga scan was normal in 10/11 sites at the first radionuclide examination after systemic therapy, indicating no active tumor, an observation supported by clinical follow-up from 6 to 72 mo. CONCLUSION: Gallium-67 scanning appears useful in the management of patients with both extragonadal and gonadal seminoma and may be useful in differentiating active disease from fibrosis in the treated patient with a post-therapy residual radiologic mass.

Adult↗
PubMed1994

Constitutive secretion of soluble interleukin-2 receptor by human T cell lymphoma xenografted into SCID mice. Correlation of tumor volume with concentration of tumor-derived soluble interleukin-2 receptor in body fluids of the host mice.

Increased serum concentration of soluble alpha-chain receptor for interleukin-2 (sIL-2R) has been noted in patients with a variety of inflammatory conditions and lymphoid malignancies including T cell leukemia and lymphoma. Elevated sIL-2R serum levels seen in lymphoid malignancies appear to correlate with the clinical stage of disease. However, because sIL-2R is produced by normal activated lymphocytes, it has been uncertain whether serum sIL-2R in such conditions is derived from tumor cells or normal immune cells responding to the tumor. To address this question, we used a model of human (CD30+) anaplastic, large T cell lymphoma transplanted into immunodeficient SCID mice. Reverse transcription polymerase chain reaction of tumor RNA showed that the tumor, designated mJB6, contains mRNA for alpha-chain of human IL-2R. Furthermore, 15 to 25% of tumor cells stained with anti-human IL-2R alpha-chain mAb. Solid phase ELISA analysis of serum samples from mice bearing mJB6 lymphoma showed high concentrations of human sIL-2R. None of the control mice without lymphoma or with human nonlymphoid tumors (prostatic carcinoma, ovarian carcinoma, and glioblastoma multiforme) showed detectable human sIL-2R. The sIL-2R serum titers of mJB6-bearing mice correlated strongly with tumor volume (P < 0.0001). Tumors as small as 0.4 to 0.8 mm3 could be detected by this method. The sensitivity of sIL-2R ELISA exceeded at least 150 times the sensitivity of conventional radioisotopic tumor detection. Total resection of mJB6 tumors resulted in complete clearance of sIL-2R from the murine serum within 48 hours with a half-life of 6 hours. Accordingly, partial resection led to a significant decrease in sIL-2R followed by gradual increase with tumor regrowth. sIL-2R was also detected in the urine of mJB6-transplanted mice. As in serum, urine concentrations of sIL-2R were proportional to tumor mass (P < 0.02). Based on these findings we postulate that malignant cells are a major source of serum sIL-2R in patients with lymphoid tumors. In addition, our data further support monitoring sIL-2R concentration in body fluids as a sensitive method to detect change in tumor volume in such patients.

Animals↗
PubMed1993

Ga-67 scintigraphy after bone marrow harvest. Significance of "sacroiliac" asymmetry in the lymphoma patient.

The importance of recognizing asymmetric Ga-67 citrate uptake in the sacroiliac region after bone marrow harvest and transplant is discussed in a case of non-Hodgkin's lymphoma. The patient underwent chemotherapy, irradiation, and autologous bone marrow transplant for stage IV disease. Ga-67 scintigraphy revealed sacroiliac asymmetry suggesting medial iliac reparative changes after bone marrow harvest. Iliac bone marrow biopsy showed no evidence of infection or of recurrent tumor. Subsequent follow-up imaging and open biopsy demonstrated lymphomatous invasion of adjacent soft tissue where initial findings were thought to represent benign, postharvest changes.

Adult↗
PubMed1993

Large-cell and immunoblastic lymphoma of the mediastinum: prognostic features and treatment outcome in 57 patients.

PURPOSE: A retrospective study was performed to define clinical characteristics and therapeutic outcome for patients with large-cell and immunoblastic lymphoma of the mediastinum. PATIENTS AND METHODS: Fifty-seven patients who presented with primary, mediastinal large-cell and immunoblastic lymphoma were retrospectively studied to determine initial sites of disease, radiologic characteristics, treatment, outcome, and factors that have prognostic significance for progression-free and overall survival. RESULTS: Fifty-six of the 57 patients had disease that was confined to sites above the diaphragm. Bulky disease and extensive intrathoracic infiltration were common in these patients. All patients were treated with intensive chemotherapy regimens, and 44% of patients received chest irradiation. The overall 5-year survival by Kaplan-Meier estimation was 50% with a freedom-from-relapse rate of 45%. Predictors of disease relapse after chemotherapy included the presence of a pleural effusion (P = .015), a number of involved extranodal sites (P < .01), and a lactic dehydrogenase (LDH) ratio > 3.0 (LDH value/upper limit of assay; P = .04) as well as an incomplete treatment response as evidenced by residual mass on chest radiograph (P = .02) or persistent gallium 67 avidity (P = .01) after chemotherapy. Predictors of decreased survival included the presence of pleural effusion (P = .001), the number of involved extranodal sites (P = .022), and a positive posttreatment 67Ga scan (P = .027). CONCLUSION: Patients with primary mediastinal large-cell and immunoblastic lymphoma have an approximate 50% chance of surviving disease-free after initial therapy. The presence of pleural effusion at presentation was associated with an extremely poor outcome. Bulk disease per se was a negative predictive factor only in patients without pleural effusions when compared with patients who did not have bulk disease. In addition, all patients with involvement of two or more extranodal sites relapsed when treated with standard chemotherapy.

Actuarial Analysis↗
PubMed1992

Gallium imaging in metastatic and recurrent soft-tissue sarcoma.

Fifty-six patients with metastatic or recurrent soft-tissue sarcoma were evaluated by 67Ga-citrate imaging. Prior to entry on the therapy protocol, 52/56 (93%) patients had true-positive 67Ga studies. Two of four patients with liposarcoma, one of twelve with leiomyosarcoma and one with an epithelioid sarcoma had false-negative studies; 89/105 disease sites (85%) were 67Ga positive, including 100% of pleural lesions, 94% in bone, 88% in the abdomen, 85% in soft tissue, 78% in lung parenchyma and 56% of liver metastases. There was significant association between 67Ga avidity and tumor grade with the exception of mesothelioma. No relationship was seen between 67Ga avidity and tumor cell type, disease site or lesion size. Following therapy, 67Ga correctly identified 11/12 sites of active disease in 8/9 patients. Mean pre- and post-therapy 67Ga avidity scores did not differ significantly. Gallium-67 appears to have an important role in the evaluation of patients presenting with either primary or metastatic soft-tissue sarcoma.

Adolescent↗
PubMed1991

Genomic sequence and expression of a cloned human carbonyl reductase gene with daunorubicin reductase activity.

Carbonyl reductase (NADPH: secondary-alcohol oxidoreductase; EC 1.1.1.184), a widely distributed NADPH-dependent enzyme considered as both an aldo-keto reductase and a quinone reductase, was cloned from a human liver genomic library and transiently expressed in COS7 cells. The gene contains 3142 bases comprising three exons and two introns. The absence of a CAAT and TATA box and the presence of a GC-rich island are characteristic of many "housekeeping" genes. Transient expression of the genomic gene in COS7 cells using an expression vector containing an SV40 origin of replication resulted in a greater than 50-fold increase in both menadione reductase activity and daunorubicin reductase activity, suggesting that both activities are derived from the same enzyme. Carbonyl reductase mRNA levels reflected enzyme activity levels in the transfected cells. Other parameters, such as pH profile, cofactor requirements, substrates, and inhibitors, were similar to those of carbonyl reductase purified by other investigators. Potential regulatory elements with consensus sequences for two GC boxes and the transcriptional activator protein AP-2 were present upstream of the transcriptional start site. Although the precise role of carbonyl reductase is unknown, the enzyme is involved in drug metabolism and in the reduction of activated carbonyl compounds. Its ability to act as a quinone reductase also implies a potential to modulate oxygen free radicals.

Alcohol Oxidoreductases↗
PubMed1990

Rat liver NAD(P)H:quinone oxidoreductase: cDNA expression and site-directed mutagenesis.

Rat liver NAD(P)H:quinone oxidoreductase cDNA was cloned and expressed in a eukaryotic cell expression plasmid containing a cytomegalovirus (CMV) promoter. Transient expression of enzyme activity and RNA transcription were measured in COS7 cells. The expressed quinone reductase has kinetic properties similar to the rat liver enzyme and is inhibited by dicourmarol, a known inhibitor of NAD(P)H:quinone oxidoreductase. Site-directed mutagenesis experiments carried out using this expression system revealed possible regions involved in NAD(P)H binding.

Amino Acid Sequence↗
PubMed1990

Leuprolide therapy for prostate cancer. An association with scintigraphic "flare" on bone scan.

The scintigraphic "flare" phenomenon on bone imaging refers to an increase in intensity of tracer uptake in sites of bone metastases and/or the appearance of "new" lesions, which occur shortly after commencement of hormonal therapy or chemotherapy for breast, prostate, or lung cancer. In this study, we observed that scintigraphic flare can occur in patients with prostate cancer following treatment with the "hormone-like" luteinizing hormone releasing hormone analog, leuprolide acetate. Twenty-six patients with prostate cancer being treated with leuprolide acetate underwent serial bone scans at three-month intervals. Five (19.2%) of the 26 patients had findings consistent with a scintigraphic flare on bone scans obtained between three and six months after initiation of therapy. These scan findings should not be confused with progression of skeletal metastases.

Antineoplastic Agents↗
PubMed1990

Bone scans with one or two new abnormalities in cancer patients with no known metastases: reliability of interpretation of initial correlative radiographs.

To determine the reliability of radiographs obtained for correlation with bone scans showing one or two new abnormalities in cancer patients without known metastases, a retrospective study of 306 scans showing such lesions was performed. Overall, 14% of the lesions proved to be malignant. The initial radiographic interpretation was normal for 43% of the new bone scan lesions; 17% of these lesions were metastases. A benign process was identified on radiographs for 38% of the abnormalities; only one (1%) was a metastasis. Twelve percent of new bone scan lesions correlated with radiographic abnormalities considered either suggestive of or consistent with metastasis, of which 24% and 71%, respectively, proved to be metastases. In cancer patients with one or two new bone scan abnormalities, correlative radiographs showing a benign abnormality are reliable. However, if the radiographs are either normal or show findings considered suggestive of or consistent with metastasis, further evaluation or follow-up is warranted.

Bone Diseases↗