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Biomedical subjects

M LaQuaglia

Publications and source records attributed to M LaQuaglia.

17 recordsLinked to original sources
PubMed2001

N7: a novel multi-modality therapy of high risk neuroblastoma (NB) in children diagnosed over 1 year of age.

BACKGROUND: The N7 protocol for poor-risk neuroblastoma uses dose-intensive chemotherapy (as in N6 protocol [Kushner et al.: J Clin Oncol 12:2607-2613, 1994] but with lower dosing of vincristine) for induction, surgical resection and 2100 cGy hyperfractionated radiotherapy for local control, and for consolidation, targeted radioimmunotherapy with 131I-labeled anti-GD2 3F8 monoclonal antibody and immunotherapy with unlabeled/unmodified 3F8 (400 mg/m2). PROCEDURE: The chemotherapy consists of: cyclophosphamide 70 mg/kg/d x 2 and a 72-hr infusion of doxorubicin 75 mg/m2 plus vincristine 2 mg/m2, for courses 1, 2, 4, and 6; and cisplatin 50 mg/m2/d x 4 and etoposide 200 mg/m2/d x 3, for courses 3, 5, and 7. 131I-3F8 is dosed at 20 mCi/kg, which is myeloablative and therefore necessitates stem-cell support. RESULTS: Of the first 24 consecutive previously untreated patients more than 1 year old at diagnosis, 22 were stage 4 and two were unresectable stage 3 with MYCN amplification. Chemotherapy achieved CR/VGPR in 21 of 24 patients. Twenty patients to date have completed treatment with 131I-3F8, and 15 patients have completed all treatment. With a median follow-up of 19 months, 18 of 24 patients remain progression-free. CONCLUSIONS: Major toxicities were grade 4 myelosuppression and mucositis during chemotherapy, and self-limited pain and urticaria during antibody treatment. Late effects include hearing deficits and hypothyroidism.

Antibodies, Monoclonal↗
PubMed2000

Local control with multimodality therapy for stage 4 neuroblastoma.

PURPOSE: To evaluate the efficacy of 21 Gy hyperfractionated radiotherapy for local control in conjunction with surgery and intensive systemic therapy for patients with Stage 4 neuroblastoma. METHODS AND MATERIALS: After achieving a partial or complete remission, 47 children, ages 1-10 years, with Stage 4 neuroblastoma were treated on four consecutive institutional protocols (N4-N7) with dose-intensive multi-agent chemotherapy, maximal surgical debulking, and hyperfractionated radiotherapy (1.5 Gy twice a day to 21 Gy). Radiotherapy fields encompassed the initial tumor volume and regional lymph nodes plus a 3-cm margin. This was followed by consolidation with either autologous bone marrow transplantation (N4 and N5) or immunotherapy (N6 and N7). RESULTS: Forty-five of 47 patients had a complete response to surgery and chemotherapy prior to radiotherapy. Five-year actuarial rates of local control, progression-free survival, and overall survival were 84%, 40%, and 45%, respectively. Among 26 patients who relapsed, 1 failed only at the primary site, 22 developed distant metastases exclusively, and 3 had both local and distant failures. There were no acute complications of radiotherapy. CONCLUSION: Hyperfractionated radiotherapy to 21 Gy, in conjunction with dose-intensive systemic therapy and aggressive surgical resection, is well tolerated and is associated with durable local control for most patients with Stage 4 neuroblastoma.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1999

Effect of low-dose radiation therapy when combined with surgical resection for Ewing sarcoma.

BACKGROUND: As an alternative to high-dose irradiation, limited surgery and low-dose irradiation have been investigated as a means to achieve local control. We retrospectively examined the clinical characteristics, treatment, and outcome for 25 patients with Ewing sarcoma treated with limited surgery and low-dose irradiation. PROCEDURE: The records of 25 patients (age 4-48 years) were reviewed who were treated between 1979 and 1996 at Memorial Sloan-Kettering Cancer Center. At the time of diagnosis, 21 of the 25 patients had prognostically unfavorable tumors including the presence of metastatic disease (n = 12), an axial primary (n = 17), and a tumor measuring greater than 8 cm (n = 18). The primary tumor was completely resected (wide local excision) in 13 patients, incompletely resected (marginal excision) in 7 patients, and biopsied only in the remaining 5 patients. The median dose of irradiation to the primary site was 30 Gy. RESULTS: With a median follow-up of 67 months (range 16-189 months) for the surviving patients, 28% failed distantly, and an additional 28% suffered from the progression of previously established metastatic disease. No patient failed locally. The median overall survival was 43 months. The actuarial overall survival at 5 years was 39% (+/-11%) for all patients and 60% (+/-14%) for patients with localized disease. CONCLUSIONS: Limited surgery and postoperative irradiation are one strategy that promises to balance the goal of achieving local control with the goal of diminishing late effects. Apart from the scenario in which radiation therapy is absolutely unnecessary, low-dose irradiation may be appropriate after considering the risk for local recurrence and overall prognosis.

Adolescent↗
PubMed1998

Emerging role of laparoscopy in the diagnosis of lymphoma.

PURPOSE: The results of laparoscopic procedures on patients with suspected or known lymphoma were analyzed to review the application and define the role of laparoscopy in lymphoma. PATIENTS AND METHODS: The hospital records of 94 patients who underwent 101 procedures between June 1993 and October 1996 were reviewed for demographic and clinicopathologic information. RESULTS: The procedure was diagnostic in 85 patients, either at primary presentation (48 patients), possible relapse (21 patients), in the course of treatment (eight patients), or of a liver lesion (eight patients). In the remaining 16 patients, it was used to stage possible intraabdominal disease. Twenty-seven patients had a previous unsuccessful diagnostic procedure. There were no operative deaths and eight postoperative complications (8%). The laparoscopy revealed non-Hodgkin's lymphoma (NHL) in 48 patients, Hodgkin's disease (HD) in 14 patients, other neoplastic conditions in six patients, and benign conditions in 33 patients. There was adequate information in all procedures in which lymphoma was diagnosed for treatment decisions. There was one false-negative and one nonresult for technical reasons. Ten patients commenced chemotherapy before discharge after a median delay of 3.5 days. In five of 24 patients (21%) with recurrent or persistent lymphoma, the precise diagnosis was significantly different from the original one. CONCLUSION: From our experience, laparoscopy can safely provide tissue samples of suspected lymphoma for full diagnostic analysis. It should be considered when percutaneous biopsy is not technically possible, when chromosomal or genetic analysis is needed for treatment decisions, or when the results of percutaneous biopsy are inadequate to make therapeutic decisions.

Abdominal Neoplasms↗
PubMed1998

Expression level, allelic origin, and mutation analysis of the p73 gene in neuroblastoma tumors and cell lines.

The novel p73 gene is a structural and, in overexpression systems, functional p53 homologue. p73 resides on chromosome 1p36.33 within a commonly deleted region in neuroblastoma (NB) and other human tumors. To evaluate p73's candidacy for a NB suppressor, we analyzed 28 primary NB tumors, 14 NB cell lines, and 5 non-NB malignant pediatric tumors. We determined the level of p73 expression and its allelic origin and searched for mutations. Fifty-one different types of normal tissues all showed very low p73 expression. Although most NB tumors expressed p73 within the normal tissue range, wild-type p73 expression levels varied widely in NB and non-NB tumors and NB cell lines with increases up to 90-fold compared with normal tissues. Importantly, the p73 gene was biallelically expressed in five of six NB tumors and three of three normal tissues. Mutation analysis of the entire open reading frame of the gene in 16 tumors (including all 6 highly expressing tumors) revealed four polymorphic sites, but no mutations. Collectively, our data argue that p73 is unlikely to be a suppressor gene inactivated during neuroblastoma development.

Alleles↗
PubMed1997

Correlation of MYCN amplification, Trk-A and CD44 expression with clinical stage in 250 patients with neuroblastoma.

In contrast to MYCN amplification, expression of either trk-A or CD44 in neuroblastoma is a favourable prognostic factor and were therefore investigated in tumours from 250 patients. One hundred and eleven localised/4s (Group 1) and 139 stage 4 (Group 2) tumours were analysed. MYCN copy number was obtained by Southern blotting or PCR amplification and was detected in 28 stage 4 tumours. Trk-A and CD44 expression was detected by immunoperoxidase staining using murine monoclonal antibodies 5C3 and L178, respectively. Expression was scored as positive (homogeneous), mixed (heterogeneous) or non-reactive (negative). Trk-A expression was found in 95% of Group 1 tumours and 49% of Group 2 tumours. CD44 expression was found in 100% of Group 1 tumours, the majority of which had a strong homogeneous expression. Lack of CD44 expression occurred in 25% of tumours, all stage 4 neuroblastoma. Of the 28 MYCN amplified tumours, 27/28 (96%) were trk-A negative, and 13/28 (46%) CD44 negative. We conclude that (1) a significant percentage of stage 4 neuroblastoma express either or both trk-A and CD44, (2) the absence of CD44 expression is highly restricted to stage 4 neuroblastoma and is associated with the lack of trk-A expression, (3) trk-A negativity among CD44-positive tumours is associated with stage 4 neuroblastoma and (4) the absence of trk-A expression is highly correlated with MYCN amplification.

Carrier Proteins↗
PubMed1995

Wild-type p53 protein undergoes cytoplasmic sequestration in undifferentiated neuroblastomas but not in differentiated tumors.

Neuroblastoma (NB), a tumor arising from the sympathetic nervous system, is one of the most common malignancies in childhood. Several recent reports on the p53 genotype found virtually exclusive wild-type status in primary tumors, and it was postulated that p53 plays no role in the development of NB. Here, however, we report that the vast majority of undifferentiated NBs exhibit abnormal cytoplasmic sequestration of wild-type p53. This inability of p53 to translocate to the nucleus presumably prevents the protein from functioning as a suppressor. Thirty of 31 cases (96%) of undifferentiated NB showed elevated levels of wild-type p53 in the cytoplasm of all tumor cells concomittant with a lack of nuclear staining. p53 immunoprecipitation from tumor tissues showed a 4.5- to 8-fold increase over normal protein levels. All of 10 tumors analyzed harbored wild-type p53 by direct sequencing of full-length cDNA and Southern blot. In addition, no MDM-2 gene amplification was seen in all 11 tumors analyzed. In contrast, no p53 abnormality was detected in 14 differentiated ganglioneuroblastomas and 1 benign ganglioneuroma. We conclude that loss of p53 function seems to play a major role in the tumorigenesis of undifferentiated NB. This tumor might abrogate the transactivating function of p53 by inhibiting its access to the nucleus, rather than by gene mutation. Importantly, our results suggest that (i) this could be a general mechanism for p53 inactivation not limited to breast cancer (where we first described it) and that (ii) it is found in a tumor previously not thought to be affected by p53 alteration.

Blotting, Southern↗
PubMed1993

A prospective, randomized evaluation of the effect of silver impregnated subcutaneous cuffs for preventing tunneled chronic venous access catheter infections in cancer patients.

OBJECTIVE: This study was performed to evaluate the effect of a silver-impregnated cuff on the incidence of catheter-related bacteremia/fungemia or tunnel tract infection in cancer patients with chronic dual-lumen tunneled venous access catheters. SUMMARY BACKGROUND DATA: Infection is a frequent and potentially life-threatening complication of tunneled chronic cuffed silastic central venous access catheters in cancer patients. Recent experience with antimicrobial silver-impregnated cuffs placed on nontunneled percutaneously inserted central venous catheters suggests that such a cuff may render the catheter less prone to infection. METHODS: The authors prospectively randomized 200 cancer patients to receive either a dual-lumen 10 French tunneled cuffed silastic central venous access catheter or the same catheter with a second more proximal subcutaneous silver-impregnated cuff. All patients then were followed prospectively for infectious morbidity until the device was removed or the patient died. RESULTS: The hazard rate for infection/day (95% confidence limits) was 0.0022 (0.0015 to 0.0030) for standard catheters compared with 0.0027 (0.0019 to 0.0037) for catheters with silver-impregnated cuffs (p = not significant). Regression analysis of infection-free interval of both catheter types shows no difference over the lifetime of catheter as well as the over the first 48 days after insertion. CONCLUSIONS: The study indicated no effect of a silver-impregnated cuff in decreasing the incidence of catheter-related bacteremias/fungemias, tunnel infections, or the spectrum of causative microorganisms involved in cancer patients with tunneled chronic venous access catheters.

Adolescent↗
PubMed1993

Osteogenic sarcoma with clinically detectable metastasis at initial presentation.

PURPOSE: Chemotherapy and surgery have improved the length of survival for patients with osteogenic sarcoma (OS) who present without metastatic disease. We reviewed our experience with patients with OS who presented with clinically detectable metastasis to determine the prognostic factors and the effects of surgery on the primary tumor and on metastatic disease. PATIENTS AND METHODS: From 1975 to 1984 we treated 62 patients who had previously untreated OS with metastasis detected at presentation. All of these patients received intensive chemotherapy that included high-dose methotrexate; doxorubicin; and bleomycin, cyclophosphamide, and dactinomycin (BCD). Selected patients also received cisplatin. The intent of surgery was resection of the primary tumor and metastatic disease. RESULTS: Survival was extremely poor; only 11% of patients survived, with a median survival of 20 months. Survival was not affected by use of preoperative chemotherapy versus immediate surgery, and did not correlate with serum lactate dehydrogenase (LDH) level, alkaline phosphatase level, or the site of the primary tumor. Survival did correlate with age, location of metastatic disease, histologic response to preoperative chemotherapy, and completeness of surgical resection of all sites of tumor. Resection of all sites of tumor identified at initial presentation was necessary for survival. CONCLUSION: OS that presents with metastatic disease has a very poor prognosis with therapy, although therapy has achieved good results for patients without metastasis detected at diagnosis. Aggressive surgical resection of tumor is necessary for survival. The use of novel therapies at initial presentation is justified with this group of patients.

Adolescent↗
PubMed1991

Myeloablative combination chemotherapy without total body irradiation for neuroblastoma.

Myeloablative treatment intensification in 25 patients diagnosed when older than 12 months of age with stage IV neuroblastoma included sequential delivery of cisplatin 120 mg/m2 x 1, hyperfractionated radiation (2,100 cGy) to the primary site and adjacent lymph nodes, carmustine (BCNU) 200 mg/m2 x 1, melphalan 60 mg/m2/d x 3 (n = 13) or thiotepa 300 mg/m2/d x 3. (n = 12), and etoposide (VP 16) 300 mg/m2/d x 3. Seventy-two hours after the last dose of VP 16, histologically tumor-free and 4-hydroperoxycyclophosphamide (4-HC; 100 mumol/L)-purged autologous bone marrow (ABMT) was infused. Acute toxicities included grade 3 to 4 oral mucositis, grade 1 to 2 diarrhea, and fevers. No patient required infusion of unpurged reserve autografts. At ABMT, 16 patients (group I) were progression-free 6.5 months to 14 months (median, 9 months) from diagnosis: seven remain progression-free 20 months to 46 months (median, 39 months) off therapy, six relapsed 4 months to 17 months post-ABMT, and three died of toxicity (candidiasis, metabolic derangement, and venoocclusive disease [VOD]). The event-free survival of group I patients is 44% at 24 months post-ABMT. Nine patients (group II) were in second remission at ABMT, including three who had relapsed after other transplant procedures: two are progression-free 24 months and 41 months off therapy, four relapsed 3 months to 12 months post-ABMT, and three died of toxicity (aspergillosis, hemorrhagic cystitis, VOD). Only one of 10 relapses involved a primary site, suggesting a beneficial effect of local radiation. In terms of survival or toxicity, an advantage for melphalan or thiotepa was not evident. Regimens such as this may prolong the survival of selected patients with poor-risk neuroblastoma, but concerns over late relapses and toxicity mandate continuing efforts to devise alternative, less risky, and more clearly beneficial approaches for definitive ablation of neuroblastoma.

Adrenal Gland Neoplasms↗
PubMed1991

Genitourinary rhabdomyosarcoma in children.

The survival rates for childhood rhabdomyosarcomas have risen from 20% to 50% with the institution of a multidisciplinary approach involving the pediatric oncologist, radiation therapist, and surgeon. Increased survival has been particularly striking in the case of genitourinary rhabdomyosarcomas, which have a more favorable prognosis than rhabdomyosarcomas occurring in other anatomic sites. By stratifying genitourinary rhabdomyosarcomas by anatomic subgroup, i.e., paratesticular, bladder or bladder-prostate, and gynecologic, insight into specific predictors of failure can be obtained. Patients judged to be high risk at diagnosis can then be selected for more intensive or novel forms of therapy.

Child↗
PubMed1990

Dose-intensive use of cyclophosphamide in ablation of neuroblastoma.

A dose-intensive, cyclophosphamide (CPM)-based chemotherapy regimen was tested in 22 children with newly diagnosed metastatic or refractory neuroblastoma. The N5 protocol consisted of four courses of CPM (140 mg/kg over 2 days), doxorubicin (45 mg/m2 over 3 days), and vincristine (0.05 mg/kg/d on days 1, 2, and 9) (CAV regimen), followed by three courses of cisplatin (40 mg/m2/d) and VP16 (150 mg/m2/d) for 3 days (PVP regimen). Courses started when the neutrophil count was 500/microliters or greater and the platelet count was greater than 100,000/microliters; most courses began by day 21. Extramedullary toxicities were mild. All patients had Grade 3 to 4 myelosuppression, yet bone marrow harvested after the N5 protocol engrafted in 11 of 11 patients whose post-N5 treatments required autologous bone marrow transplantation (ABMT). Among 14 previously untreated patients, the N5 plus surgery achieved 9 complete remissions (CR) or very good partial remissions (VGPR) and 3 partial remissions (PR). An additional patient achieved CR with CAV, but experienced a recurrence in the bone marrow after PVP. The sole previously untreated patient whose bone marrow disease did not resolve received courses of the N5 at prolonged intervals (for nonmedical reasons). Among eight patients with progressive (six patients) or refractory (two patients) disease while on other, lower dose regimens, the N5 plus surgery achieved five CR/VGPR, two PR, and one minor response (MR). In conclusion, dose-intensive use of CPM has tolerable toxicity and does not preclude autografting; when administered in conjunction with other cytotoxic agents, it is highly effective against metastatic neuroblastoma and causes regressions of disease resistant to less intensive regimens. This approach plus surgery reliably achieves a minimal disease state that may be amenable to definitive ablation with relatively nontoxic therapies.

Adolescent↗
PubMed1990

Prognostic significance of regional lymph node involvement in childhood extremity rhabdomyosarcoma.

Thirty-four patients with extremity rhabdomyosarcoma were treated at Memorial Sloan-Kettering Cancer Center during the years 1970 to 1987. The regional lymph node status at diagnosis was histologically confirmed in 27 patients. Of these 27 patients, there were 20 males and 7 females, ranging in age from 6 months to 22 years (median 10 years). The primary tumor was located in the upper and lower extremity in 11 and 16 patients, respectively. The histologic subtypes included embryonal in 13 patients and alveolar in 14 patients. Fourteen patients had no evidence of regional lymph node involvement (N0) and 13 patients had lymphatic metastases (N1). All patients were further staged according to the extent of surgical resection, the local invasiveness and size of the primary tumor, and the presence (M1) or absence (M0) of distant metastases. With a median follow-up time from diagnosis of 9.2 years (minimum 5.3 years), the overall survival was 48% (13/27): N0, 12/14 and N1, 1/13 (P = .0002). Excluding those patients with M1 disease, the survival rate was: N0, 11/12; N1, 1/10 (P = .0001). The first site of relapse in the M0 patients was distant metastases in 8/10 cases. Our results suggest that regional lymph node involvement at diagnosis is an important prognostic factor in extremity RMS. Its presence appears to be associated with a high incidence of relapse in metastatic sites and poor survival outcome.

Adolescent↗
PubMed1990

Radiocurability of microscopic disease in childhood rhabdomyosarcoma with radiation doses less than 4,000 cGy.

In an attempt to evaluate the radiocurability of microscopic disease in childhood rhabdomyosarcoma (RMS) with total tumor doses of less than 4,000 cGy, we performed a retrospective analysis of all patients with microscopic residual RMS who were treated at the Memorial Sloan-Kettering Cancer Center (MSKCC) during the years 1970 to 1987. There were 32 patients ranging in age from 3 months to 22 years (median, 6 years) with microscopic residual of either (1) a localized primary tumor (MSKCC, stage IB; Intergroup Rhabdomyosarcoma Study [IRS] group IIA), 19 patients; or (2) an involved lymph node region with the primary tumor completely resected (MSKCC stage III; IRS group IIC), 13 patients. Twenty-nine of the 32 patients presented with embryonal histology. All patients were treated with combination chemotherapy (CT) and megavoltage external beam radiotherapy (RT). The RT was delivered in either conventional fractionation of 180 to 200 cGy daily (30 patients) or hyperfractionation of 150 cGy twice daily (two patients). Fifteen patients received RT doses of less than 4,000 cGy with a range of 3,000 to 3,600 cGy and a median value of 3,100 cGy; 17 patients received 4,000 cGy or more with a range of 4,000 to 6,000 cGy and a median value of 4,600 cGy. With a median follow-up of 11 years, the relapse-free survival was 25 of 32 patients (less than 4,000 cGy, 12 of 15; greater than or equal to 4,000 cGy, 13 of 17). The RT local control rate was 30 of 32 (less than 4,000 cGy, 14 of 15; greater than or equal to 4,000 cGy, 16 of 17 [P = .94]). Our results suggest that radiation doses of below 4,000 cGy, when combined with effective multiagent CT, may be sufficient for local control of microscopic disease in childhood embryonal RMS.

Adolescent↗
PubMed1986

Can fetal and newborn allografts survive in an immunocompetent host?

This study explores methods of prolonging allograft survival by varying the ontogeny of the donor tissue (fetal, newborn, and adult), and the recipient (newborn and adult) in a series of outbred Sprague-Dawley rats. Allografts of renal or adrenal tissue (1 mm2) were implanted under the renal capsule of the recipient animal. Six experimental groups were constructed with the adult as the recipient in the first three, and four-to six-day-old newborn rat pups in the last three groups. A total of 212 animals were grafted and the animals were killed between 7 and 83 days later, and we carried out morphometric and histologic analyses of all grafts. In Group I (adult donor----adult host), all 17 grafts implanted for ten days or longer were completely rejected. In Group II, newborn tissue was implanted into 23 adults. By nine days after implantation, 17 grafts were fully rejected and the average graft had decreased in size by 68% +/- 78.7% (P less than .05 compared with their initial size). In contrast, when fetal renal or adrenal grafts were implanted into 93 adults (Group III) we saw a 17.6 +/- 9.7 fold increase in graft size when recipients were killed at least 7 days after implantation (P less than .05 compared with their initial size). When we used the newborn as a recipient, we found that all 20 adult grafts (Group IV) were rejected within 10 days. When newborn tissue was implanted into 15 newborns (Group V) all 15 animals rejected their grafts within ten days.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Glands↗
PubMed1986

Sertoli cell production of müllerian inhibiting substance in vitro.

Sertoli cell cultures were monitored for müllerian inhibiting substance with a solid phase radioimmunoassay. Sertoli cells from newborn calf testes were placed in defined media free of serum in monolayer culture after treatment with trypsin-collagenase followed by gravity separation. Immunoreactive müllerian inhibiting substance was detected in the culture media of Sertoli cells but not National Institutes of Health 3T3 cells. To verify that the Sertoli cells were intact, cyclic adenosine monophosphate levels were determined after follicle-stimulating hormone stimulation. Cyclic adenosine monophosphate levels were elevated in Sertoli cells but not National Institutes of Health 3T3 cells. The newborn calf Sertoli cell culture provides a useful system in which to study factors affecting müllerian inhibiting substance production and release, and documents this substance as another reliable marker for the Sertoli cell. Müllerian inhibiting substance levels also could be measured in media beneath testicular fragments in organ culture, and were increased and prolonged in comparison to müllerian inhibiting substance release from Sertoli cell monolayer cultures. Modulation of müllerian inhibiting substance release from monolayer and organ cultures then was attempted. Neither gonadotropin nor steroid additions affected the release of müllerian inhibiting substance during 24 to 72 hours in organ or tissue culture. We are using the müllerian inhibiting substance radioimmunoassay to monitor attempts to immortalize a Sertoli cell line capable of continuous müllerian inhibiting substance production using viral deoxyribonucleic acid transfection techniques.

Animals↗