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T K Das Gupta

Publications and source records attributed to T K Das Gupta.

At least 19 recordsLinked to original sources
PubMed1997

Phase I evaluation of interleukin-2-transfected irradiated allogeneic melanoma for the treatment of metastatic melanoma: appendix 1: protocol.

A cell line (UISO-H-MEL-2) was established from the neoplastic cells of a patient with malignant melanoma during the natural course of the patient's treatment. The melanoma cells express defined MHC Class I histocompatibility determinants including determinants specified by the HLA-A2 Class I allele, along with a common melanoma-associated T-cell epitope derived from the tyrosinase gene. The gene for human interleukin-2 (IL-2) was transduced into the cells with a provirus (pZipNeoSVIL-2), packaged in GP + envAM12 cells. Integration of the IL-2 gene into genomic DNA of the transduced cells and its expression were established. The IL-2-secreting cell line (UISO-H-MEL-2-IL-2) was found to be free of recombinant retroviruses and other infectious agents. The IL-2-secreting cells will be subjected to 5000 rads X-irradiation and administered to 12 informed patients with metastatic malignant melanoma in a Phase I toxicity study. The dose of X-irradiation was sufficient to inactivate one hundred percent of the cells, but insufficient to completely inhibit IL-2 synthesis during a fourteen-day period of analysis. Patients who have failed all standard forms of treatment will become eligible for inclusion in the study if they develop metastatic melanoma, and if their tumor cells express products of the tyrosinase gene. The patients will differ with the cellular immunogen at no less than three of six MHC Class I alleles, but will share identity at the HLA-A2 Class I allele. The patient's antimelanoma immune response to the injected cells will be determined by both in vivo and in vitro parameters. Background studies performed in inbred mice indicate that X-irradiated IL-2-secreting cells that express both melanoma-associated antigens and allogeneic Class I histocompatibility antigens are more antigenic in terms of their capacity to induce an antimelanoma response than X-irradiated IL-2-secreting melanoma cells. Of significance for the future potential of this form of therapy in melanoma patients, the period of survival of mice was established melanoma treated with the IL-2-secreting allogeneic cells was significantly (P < 0.001) longer than that of untreated animals, or animals treated with X-irradiated melanoma cells. An analogous protocol was reviewed and approved by the Recombinant DNA Advisory Committee of the National Institutes of Health.

Cancer Vaccines↗
PubMed1997

Evaluation of newer prognostic markers for adult soft tissue sarcomas.

PURPOSE: In addition to tumor size, grade, location, and the presence of metastases, other factors may be useful in prognostication for adults with soft tissue sarcoma (STS). This study examines the relationship of MDR-1 mRNA, p-glycoprotein (P-gp), Ki-67 expression, and DNA content expression to clinical outcome in adults with STS. PATIENTS AND METHODS: Snap-frozen STS specimens from 65 patients were analyzed and compared with clinical outcomes. Immunohistochemistry was performed for the Ki-67 antigen and P-gp. DNA content was determined using the Feulgen reaction and quantitated using image analysis. MDR-1 mRNA expression was determined using a reverse-transcriptase polymerase chain reaction (RT-PCR)-based assay. RESULTS: P-glycoprotein expression was found by immunohistochemistry in 48% of cases with 5-year overall (54% v 14%, P = .07) and disease-free survival rates (32% v 18%, P = .039) higher in high-grade tumors that did not express P-gp. MDR-1 mRNA was detected in 51% of cases and no patient with high levels of MDR-1 mRNA expression was a long-term survivor. Patients with diploid tumors had significantly better survival than those with nondiploid tumors (51% v 31%, P = .03). High levels of Ki-67 were associated with poorer overall survival (46% v 31%, P = .04). On multivariate analysis, American Joint Committee on Cancer (AJCC) staging, DNA content, Ki-67, and P-gp staining were significant prognostic factors for 5-year overall and disease-free survival. CONCLUSION: P-gp expression, high-level Ki-67 expression, and nondiploid DNA content are independent prognostic indicators that correlate with poor outcomes in STS patients. However, MDR-1 mRNA was not found to be predictive of survival. These newer markers are useful additions to AJCC staging for prognostication for patients with STS. Such markers may be useful in selecting high-risk STS patients who could benefit from systemic adjuvant therapy.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1996

Beta3 integrin expression in melanoma predicts subsequent metastasis.

Previous studies have suggested that differential expression and/or activation of integrins facilitates metastatic progression in murine and human melanoma. While recent data show that the integrin alphavbeta3 is involved in tumor angiogenesis and that tumor growth may be abrogated by alphavbeta3 inhibitors in vitro, the clinical significance of beta3 integrin expression in human malignant melanoma is not known. To assess the prognostic value of beta3 integrin expression, we examined primary cutaneous melanomas from 160 patients followed for a mean of 98 months or until death. We quantified the percentage of tumor area stained with beta3 integrin Ab CD-61 using an image analyzer. beta3 integrin expression was detected in 107/160 primary melanomas (69%). beta3-integrin-positive (beta3+) tumors were thicker (mean 2.98 +/- 0.3 mm) than beta3-integrin-negative (beta3-) melanomas (mean 1.64 +/- 0.2 mm) (P = 0.002). Patients with beta3+ melanomas were more likely to relapse (57/107, 53%) and to die from disease (45/107, 42%) than those with beta3- tumors (6/53, 11%; and 4/53, 8%, respectively) (P < 0.001). Overall survival was greater for beta3- than for beta3+ patients (mean 102 +/- 9 vs 69 +/- 6 months) (P = 0.001). These data show that beta3 integrin expression in primary cutaneous melanoma predicts subsequent metastatic progression. Further study of beta3 integrins in the development of melanoma metastases may yield new therapeutic strategies, as well as prognostic information, for the treatment of this cancer.

Antigens, CD↗
PubMed1995

Acral lentiginous melanoma.

OBJECTIVE: To analyze whether the histologic subtype acral lentiginous melanoma confers independent prognostic significance. DESIGN: Case series retrospective review. SETTING: Academic surgical practice. PATIENTS OR OTHER PARTICIPANTS: Fifty-six patients with histologically confirmed acral lentiginous melanoma identified from patients with malignant melanoma consecutively treated by the faculty of the Department of Surgical Oncology at the University of Illinois at Chicago. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Lymph node metastases, disease-free survival, and overall concurrent or subsequent survival. RESULTS: The average age of our patients with acral lentiginous melanoma was 61.1 years. Thirty-four (61%) were white, and the remaining 22 (39%) were African-American, Hispanic, or Asian. Thirty (54%) were male and 26 (46%) were female. The primary tumor occurred on the lower extremity in 46 (82%) of the cases and on the upper extremity in the remaining 10 (18%). Twenty-four primary tumors (43%) were greater than 4.00 mm thick. Analyzed by means of a logistic regression model, the rate of lymph node metastases did not significantly differ among patients with acral lentiginous melanoma, superficial spreading melanoma, and nodular malignant melanoma. Furthermore, when corrected for tumor thickness, disease-free and overall survival were the same for the three histologic groups. Multifactorial analysis identified only thickness as a prognostic variable for disease-free survival and overall survival. CONCLUSIONS: Despite the greater age, diverse ethnic background, and distinctive tumor characteristics of our patients with acral lentiginous melanoma, this histologic subtype does not, in itself, affect the outcome of these patients.

Aged↗
PubMed1995

Beta 1 integrin expression in malignant melanoma predicts occult lymph node metastases.

BACKGROUND: Elective lymph node dissection for malignant melanoma is still controversial. Experimental studies suggest that differential expression, activation, or both of beta1 integrins facilitate melanoma metastases. However, the clinical significance of beta1 integrin expression in human melanoma is unclear. METHODS: We examined primary cutaneous melanomas from 76 patients undergoing elective lymph mode dissection. We quantified the percentage of tumor area stained by beta1 integrin antibody with an image analyzer. RESULTS: beta1 integrin was expressed in all 23 primary tumors from patients with pathologically positive lymph nodes (LNs) but in only 14 (26%) of 53 cases with pathologically negative nodes (p < 0.001). No patients with beta1 integrin-negative tumors had LN involvement, whereas 23 (62%) of 37 patients with beta1 integrin-positive tumors had LN metastases (p < 0.001). Furthermore, 21 (91%) of 23 cases with LN metastases but only 4 (8%) of 53 cases without had beta1 integrin staining of 10% or more of tumor area (p < 0.001). CONCLUSIONS: Our study is the first to show a correlation between expression of a molecular marker in the primary cutaneous melanoma and likelihood of regional LN metastases. beta1 immunostaining of 10% or more of tumor area reliably predicts patients most likely to harbor occult LN metastases and likely to benefit from ELND.

Adult↗
PubMed1995

Overexpression of mutant p53 and c-erbB-2 proteins and breast tumour take in mice.

We established a panel of 17 xenografts from primary human breast carcinomas. We examined which characteristics of the original tumours and the xenografts facilitate growth in animals. Tumours expressing medium or strong immunoreactivity for p53 protein had significantly (P < 0.05) higher incidence (92%) of in vivo tumour take than those showing weak or negative immunoreactivity (9.1%). No such association was observed between either c-erbB-2 or epidermal growth factor receptor (EGFR) expression in the original tumours and their in vivo tumour take. Following subcutaneous (s.c.) transplantation of original breast tumours or established xenografts, 7/17 tumours showed metastatic disease spread to distant sites (mainly lungs). This study suggests that selective growth of highly aggressive tumours occurs during in vivo propagation of malignant tumours, and these tumours will be of particular interest in evaluating various chemotherapeutic agents for breast cancer management.

Adult↗
PubMed1994

Melanoma recurrence in a previously dissected lymph node basin.

OBJECTIVES: To retrospectively assess whether completeness of node dissection has any bearing on regional control in cutaneous melanoma and to examine the efficacy of a subsequent dissection in patients with isolated nodal recurrence. DESIGN: Case series, 18-month minimum follow-up. SETTING: Academic surgical practice. STUDY PARTICIPANTS: Patients with cutaneous melanoma who had undergone a regional node dissection and subsequently developed recurrence in the same nodal basin in which a lymphadenectomy had been performed with no evidence of distant metastases. Of 1030 instances of regional node dissection, 28 met these criteria. MAIN OUTCOME MEASURES: Nodal recurrence in the previously dissected lymph node basin as the only site of recurrence and survival following a subsequent lymph node dissection. RESULTS: The 28 instances of isolated nodal recurrence represent a regional failure rate of 2.7%. In those cases where the first dissection was performed within our division, the rate is 0.8%. Recurrence for cervical, axillary, or inguinal sites was similar. In 71% of the cases, more than one node was positive at the time of recurrence. Four patients have shown disease-free survival greater than 3 years following a subsequent lymphadenectomy. CONCLUSION: Node dissection is a therapeutic procedure and, therefore, must consist of complete lymphadenectomy with meticulous attention to surgical detail. Approached in this fashion, only a small subgroup of patients will show recurrence in a previously dissected nodal basin, a few of whom can be salvaged by a second dissection.

Adult↗
PubMed1994

Fibrosarcoma of the head and neck.

Fourteen adult patients with fibrosarcoma of the head and neck were treated by the Division of Surgical Oncology at the University of Illinois and Cook County Hospitals. All patients had a mass in the head and neck area, and four patients (29%) had tumors in a burn scar or in a field of irradiation. The 2-, 5-, and 10-year disease-free rates were 57%, 57%, and 50%, respectively, with overall survivals of 79%, 71%, and 57%, respectively. The median survival was significantly higher for patients with low-grade tumors than for patients with high-grade lesions (P < 0.05). Wide surgical excision was the mainstay of therapy, with re-excision considered for some patients with locally recurrent disease. Aggressive treatment can afford fibrosarcoma patients good long-term therapeutic results.

Combined Modality Therapy↗
PubMed1994

Prognostic significance of nucleolar organizer regions (NORS) in malignant melanoma.

Nucleolar organizer regions (NORs) are loops of ribosomal DNA (rDNA) in the nucleolus and are associated with acidic proteins. They are seen in routinely processed paraffin sections by using a one-step colloidal silver (Ag) staining method; they appear as black dots termed "AgNORs". The quantitative assay of AgNORs has been used to differentiate benign from malignant neoplasms. Melanocytic lesions differ significantly in AgNOR counts between malignant melanoma and nevi. However, conflicting results have been reported as to AgNORs' prognostic value in melanoma. A recent study showed AgNOR counts to be a more accurate prognostic indicator than Breslow's thickness. In this study, we counted the AgNORs in 26 patients with primary cutaneous melanomas (CMM) between 2.0 mm and 2.5 mm thick. Of these, 14 are alive without disease (AN) at 5 years after diagnosis (group 1) and 12 are dead of disease (DD) in less than 5 years (group 2). The AgNORs were scored in 30 nuclei per tumor, and the means were calculated. For group 1, the mean number of AgNORs per nucleus was 6.88, ranging from 3.73 to 12.70. For group 2, the mean number was 6.97, ranging from 3.63 to 11.67. Statistical analysis using analysis of variance (ANOVA) showed no significant difference between the groups (p = 0.33). In our study, AgNOR counts did not prove to be of prognostic value in malignant melanoma.

Adult↗
PubMed1994

Forequarter amputation for soft tissue tumors.

Forequarter amputation is a radical surgical procedure initially described for the treatment of traumatic injuries in 1908. This procedure has been used more recently in the treatment of soft tissue tumors. This report describes the experience in the Division of Surgical Oncology at the University of Illinois over a 20-year period. Between 1970 and 1991, 10 patients underwent forequarter amputations for malignant disease. Nine of these patients had soft tissue tumors and one a malignant melanoma. Four patients underwent amputation as primary treatment of their tumor, and six underwent the procedure as treatment for recurrent tumor. All patients are presently alive with a mean follow-up of more than 10 years. Three patients had recurrent tumor after the forequarter amputation. One local failure was salvaged with a chest wall resection, and two patients had distant failure. Forequarter amputation remains an effective procedure for local control of tumors of varying histology involving the shoulder girdle and upper arm. The most common indication for this procedure is a recurrent soft tissue tumor for which limb sparing procedures are not applicable. Forequarter amputation should remain a rarely used, but important, surgical option for the treatment of patients with soft tissue tumors.

Adolescent↗
PubMed1993

The use of daunomycin-antibody immunoconjugates in managing soft tissue sarcomas: nude mouse xenograft model.

Analysis of human fibrosarcoma cells exposed to radiolabeled monoclonal antibody 19-24, which recognizes sarcoma-associated antigen p102, revealed that over 54% of the cell surface-bound radioactivity was internalized. No modulation of cell surface p102 antigen by monoclonal antibody 19-24 was observed in human fibrosarcoma cells. Monoclonal antibody 19-24 coupled to daunomycin via a dextran bridge was found to be most effective. In different preparations, the daunomycin:total protein molar ratio ranged from 1.9 to 6.1. In vitro cytotoxicity studies using human fibrosarcoma cells showed that, at 10 micrograms/ml concentration, this immunoconjugate was 79.4% as efficient as free daunomycin and, at 1 microgram/ml concentration, 36.8% as efficient. Control nonspecific murine monoclonal antibody P3 immunoconjugates were relatively ineffective. The distribution of 14C-Adriamycin, 125I-labeled monoclonal antibody 19-24, and 125I-labeled 19-24 immunoconjugate was also evaluated over a 24-h period in tumor and normal tissues of athymic mice bearing a human fibrosarcoma xenograft. Poor uptake of radiolabeled Adriamycin by the tumor tissue was observed. The level of 14C radioactivity in the tumor tissue never exceeded 1% of the total injected dose and was 24.8-fold lower than the radioactivity found in the spleen tissue. Tumor tissue uptake of radiolabeled monoclonal antibody 19-24 was characterized by the high tumor tissue:blood ratio of 1.62 +/- 0.28 (SD). However, for monoclonal antibody 19-24 immunoconjugates, this ratio decreased to 0.66 +/- 0.05, which was still higher than normal (liver, 0.48 +/- 0.02; lung, 0.48 +/- 0.07; spleen, 0.28 +/- 0.01) or nonspecific monoclonal antibody P3 immunoconjugates (0.22 +/- 0.03). Thus, it appears that, compared to free daunomycin, monoclonal antibody 19-24 immunoconjugates may be more efficient and less cytotoxic to normal tissues.

Animals↗
PubMed1993

Preoperative multimodality treatment for soft tissue sarcomas.

BACKGROUND: Frequently, soft tissue sarcomas (STS) do not present until they are large, thus making local control difficult. Consequently, different methods of preoperative cytoreduction should be evaluated. METHODS: This study evaluated a 10-day preoperative regimen of intraarterial doxorubicin (10 mg/m2/d), with concomitant radiation therapy (25 Gy), administered to 55 adult patients with either Stage T2 (n = 41) or distal Stage T1 (n = 14) STS. Seven of the tumors were low grade. All patients were treated by the Division of Surgical Oncology at the University of Illinois between 1978-1991. RESULTS: This regimen was successful and obviated the need for amputation in 47 patients who underwent wide soft tissue excision, an initial limb-salvage rate of 87%. Complications related to the therapy occurred in 26% of patients, which resulted in additional operative procedures in 7%. The mean follow-up time was 94 months. The 5-year overall survival rate was 69%, with a disease-free survival rate of 51%. Local control was unsuccessful in 15% of the patients. Three additional patients required amputation for recurrent disease (n = 2) or complications of therapy (n = 1), resulting in an ultimate limb-salvage rate of 81%. CONCLUSIONS: The long-term results of this preoperative protocol for adults with limb-threatening STS appears to justify the utilization of a multimodality approach. This preoperative regimen was useful in minimizing limb loss in patients with limb-threatening STS. However, intraarterial doxorubicin administration is associated with significant morbidity, and its role in multimodality treatment of STS requires further clarification.

Adolescent↗
PubMed1993

Monocyte-macrophage lineage of giant cell tumor of bone. Establishment of a multinucleated cell line.

METHOD: A new neoplastic cell line, UISO-GCT-1, was established from a giant cell tumor of the right tibia in an 18-year-old man. Immunohistochemical, cytogenetic, ultrastructural, and growth studies were performed. RESULTS: Multinucleated giant cells (> 4-6 nuclei/cell) persisted in a culture relatively late in passage (passage 17), which is unique in cell lines of giant cell tumor of bone. Mononuclear and multinucleated cells in monolayer culture expressed vimentin and tartrate-resistant acid phosphatase and reacted with monoclonal antibodies to CD13 and CD68, suggesting a monocytic-macrophage origin of these cells. Mononuclear and multinuclear cells also selectively expressed high molecular weight cell membrane antigens specifically associated with soft tissue sarcomas and osteosarcomas. Karyotypically, UISO-GCT-1 cells were hypodiploid, hypotetraploid, and multiploid, with more than 200 chromosomes per mitosis present in some cells. Other chromosomal aberrations observed included ring chromosomes, double minutes, translocations, multiple fragments, and multiradials. CONCLUSION: Collectively, observations of this study suggest that karyotypically abnormal giant cell tumors of bone arise from a monocyte-macrophage lineage and subsequently express an antigenic profile similar to malignant mesenchymal tumors.

Adolescent↗
PubMed1993

Pediatric soft tissue sarcomas of nonmyogenic origin.

Nonrhabdomyosarcoma soft tissue sarcomas (NRSTS) are relatively rare tumors, which nonetheless constitute 50% of the soft tissue sarcomas seen in the pediatric population. The prognosis for these tumors is good, with 92% of patients in our series alive and 61% free of their disease at 5 years follow-up. The most important prognostic factor among our 35 patients was the grade of the tumor. More than 70% of our patients with grade I or II lesions are disease-free at 5 years, compared to only 39% of patients with grade III lesions. The patients with the best outlook are those who can be treated with surgery alone as the definitive care for this disease. Resection remains the primary treatment modality in NRSTS, whereas, unlike the treatment of rhabdomyosarcomas, the value of radiation therapy and chemotherapy in treating NRSTS remains undefined.

Child↗
PubMed1993

MDR-1 expression in metastatic malignant melanoma.

Metastatic malignant melanoma (MMM) carries an ominous prognosis. This poor prognosis is due in part to the remarkable resistance of MMM to a wide variety of antineoplastic agents. One common mechanism of resistance to chemotherapy is that of multidrug resistance (MDR) which is mediated by the MDR-1 gene. Previous efforts to determine MDR-1 expression in MMM have all failed to show expression using relatively insensitive immunohistochemical techniques. The purpose of this study is to evaluate the incidence of MDR-1 expression in MMM using a highly sensitive polymerase chain reaction (PCR)-based assay. Twenty-two clinical snap-frozen MMM specimens were analyzed. Total cellular RNA was extracted and quantitated from which cDNA was synthesized. Sequences of MDR-1 and beta 2-microglobulin (internal control) cDNA were coamplified using PCR. The relative yield of the MDR-1-specific PCR product was quantitated relative to that of a standard series of cell lines with known MDR-1 expression. Analysis revealed that 45% of MMM expressed MDR-1 at low levels. None of the tumors expressed high levels of MDR-1. Overall survival, disease-free survival, thickness of primary lesion, histology, and sex were not found to correlate with MDR-1 expression. We conclude that MDR-1 is frequently expressed at low levels in MMM. However, this incidence of MDR-1 expression suggests that non-MDR mechanisms of drug resistance are dominant in MMM. Further studies will be required to determine if MDR-1 expression is of clinical significance in MMM.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1993

Localization of sarcoma xenografts in nude mice with indium-111-labeled monoclonal antibodies.

A labeling method utilizing modified carbohydrate moieties in antibody heavy chains as radionucleotide binding sites was evaluated. Murine anti-sarcoma monoclonal antibody (MAb 19-24) was labeled with Indium-111 (111In) using this technique and subcutaneous human sarcoma xenografts were successfully localized in nude mice. A nonspecific monoclonal antibody BL-3 was used as a negative control. Tumor-to-blood ratios of radioactivity in the mice injected with 111In-labeled MAb 19-24 were significantly (P < 0.05) higher than those obtained with nonspecific MAb BL-3. Calculations of percentage injected dose of radioactivity per gram tissue showed relatively high specific uptake of MAb 19-24 in sarcoma xenografts. Radioactivity cleared from the blood rapidly and hepatic uptake of 111In-labeled antibodies was found to be relatively low. Biodistribution studies in normal mice with 111In-labeled antibodies showed only blood pool activity with no significant concentration of activity into organs. Therefore, immunoreactivity of the antibodies was retained after 111In-labeling utilizing this new technique, allowing specific binding of radiolabeled MAb to tumor xenografts with relatively low hepatic uptake.

Animals↗
PubMed1993

Growth and metastasis of human breast carcinomas with Matrigel in athymic mice.

Immunodeficient athymic mice with human tumor xenografts provide an important in vivo experimental model for cancer research. However, only a limited number of tumor types grow in these animals. For human breast carcinomas, the incidence of tumor-take is 6-15%. Recently, increased incidence of xenograft development in mice has been reported for various human tumors when the tumors were coinjected with Matrigel. We studied the development of human breast carcinoma xenografts in athymic mice with and without coinjection of Matrigel. Tumors developed in only 7.3% of enzyme-dispersed tumors injected subcutaneously in saline solution alone. None of these tumors metastasized to distant sites. On the other hand, 50% of enzyme-dispersed tumors coinjected with Matrigel developed xenografts; four out of five of these tumors metastasized to distant sites. Our data from the recent study suggest that, in athymic mice, Matrigel not only enhanced breast tumor growth but also facilitated tumor metastasis.

Animals↗