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Harold J Wanebo

Publications and source records attributed to Harold J Wanebo.

5 recordsLinked to original sources
PubMed2003

Mucosal melanomas.

Cutaneous malignant melanoma is a common malignancy and has been increasing at an alarming rate in the United States. Sun exposure is a well-known risk factor related to this disease and much is understood regarding the etiology and epidemiology of cutaneous melanomas. In contrast, primary mucosal melanomas represent an extremely rare malignancy and do not have the same risk factors or behavior patterns. They occur in areas that have no sun exposure and solid predisposing risk factors have not been identified, making this disease very difficult to diagnose or screen for. It is usually diagnosed at a later stage and carries a poor prognosis. Identifying the differences between a primary lesion and a metastatic melanoma is often challenging, because of the lack of definitive criteria, both pathologically and clinically. The rich vascular and lymphatic network surrounding these lesions may be responsible for their aggressive behavior and poor prognosis. In addition, the obscure locations where mucosal melanomas occur are an obvious reason why these lesions often go unnoticed until symptoms develop. Recent literature has raised significant questions regarding recommended treatment strategies. Earlier reports advocated radical surgery as the mainstay of therapy; however, local recurrence and survival were unchanged whether radical surgery or local excision was performed, and the most recent data are favoring the conservative approach when appropriate. Unfortunately, a multitude of adjuvant therapies have been tried without any success. Adjuvant radiotherapy plays a role when combined with surgery, particularly in the head and neck region and female genitalia, but this is reserved for nodal and locoregionally advanced disease and has had no effect when used as a prophylactic method. It is difficult to make significant advances in treatment strategies because of the rarity of the disease. As an example, one in 75 persons born in the year 2000 will develop cutaneous melanoma in his lifetime, compared with four cases per ten million people diagnosed with mucosal melanoma per year in the United States. Possible new therapies based on new biologic and immunologic findings may have future promise on being able to impact this disease. Until then, this aggressive tumor continues to have a poor prognosis, and surgical resection continues to be the mainstay of primary therapy.

Combined Modality Therapy↗
PubMed2002

Changing patterns of failure of head and neck cancer.

BACKGROUND: With the increased use of neoadjuvant therapy for advanced stage squamous cell carcinoma of the head and neck, we have observed an apparent change in the pattern of failure from predominantly locoregional sites to distant metastases. We reviewed the patterns of failure in cancers of the oral cavity, oropharynx, and larynx at our institution during the last decade. OBJECTIVE: To determine whether there has been a significant change in the patterns of recurrence from the historical locoregional failure to distant sites, and whether this change is associated with the increased use of multimodality therapy. METHODS: We reviewed cancer registry data on patients with squamous cell carcinoma of the head and neck diagnosed between January 1, 1988, and December 31, 1999. Sites included the oral cavity and oropharynx (including the tongue, floor of mouth, retromolar trigone, gingiva, tonsil, and lip) and larynx. RESULTS: Among 432 patients with squamous cell carcinoma of the head and neck, 280 (65%) had oral cavity and oropharyngeal cancers, and 152 (35%) had laryngeal cancers. Overall, 19% developed locoregional recurrence, and 8% developed distant failure. Although locoregional failure for oral cavity and oropharyngeal squamous cell carcinoma decreased from 26% to 16% from 1988-1993 to 1994-1999, distant failure increased significantly from 3% to 8%. During these periods, multimodality therapy was used in 62% of oral cavity and oropharyngeal cancers, and this rate remained essentially unchanged. For laryngeal cancer, locoregional and distant failure remained stable at 18% and 9%, respectively. In these laryngeal cancers, the use of multimodality therapy decreased from 60% to 46%, but this difference was not statistically significant (P =.43). CONCLUSIONS: Although locoregional control in oral cavity and oropharyngeal cancers has improved significantly with the use of multimodality therapy, the incidence of distant failure has doubled. In laryngeal squamous cell carcinoma, the patterns of failure have not changed significantly.

Adolescent↗
PubMed2002

Synergistic effect of interleukin-2 and a vaccine of irradiated melanoma cells transfected to secrete staphylococcal enterotoxin A.

We have previously reported that immunization of mice with melanoma cells transfected to secrete the superantigen, Staphylococcal enterotoxin A (SEA), increased the production of antibodies to the B700 melanoma antigen, stimulated the production of endogenous interleukin 2 (IL-2), activated the expression of CD4, CD8 and CD25 T cell markers and enhanced NK cell activity. Now we show that immunization of mice with a vaccine of irradiated sea-transfected melanoma cells coupled with IL-2 therapy was even more effective in inhibiting the growth of primary melanoma tumors and the development of lung metastases than was the irradiated melanoma cell vaccine alone or IL-2 alone. The morphological and immunological effectiveness of the therapy was dose-dependent on IL-2.

Animals↗
PubMedDate not supplied

Capacity of murine IL-12 to inhibit the development of primary melanoma tumors and to prevent lung metastases in the melanoma-challenged mice.

Interleukin-12 (IL-12) has the capacity to activate cytotoxic lymphocytes, stimulate natural killer cells, induce the production of INF-gamma, and be synergistic with IL-2. We have evaluated this cytokine in an experimental model for metastatic melanoma that approximates the major clinical stages of metastatic dissemination. To develop primary melanoma tumors, mice were injected subcutaneously with 5 x 10(5) cells in a volume of 25 microliters into the middle of the tail (11). In a month, mice were started to be treated for 4 weeks with recombinant murine IL-12 (R mIL-12) at the following doses: 0, 0.5, 2.5, 5.0, 15.0, and 50 micrograms/kg. Diameters of the primary melanoma tumors were measured at weekly intervals. At the end of 13 weeks (9 weeks from the start of treatment with R mIL-12), all surviving mice were sacrificed. Pathological examination of lung metastases (macroscopy) was done with all dead or sacrificed mice. Treatment of mice bearing melanoma at a dose of 300 ng/mouse (15 micrograms/kg) inhibited development of primary tumors in 40% of mice. The primary tumor diameters were significantly lower in the group treated with 300 ng/mouse (15 micrograms/kg) in comparison to controls. At the end of the observation period, groups treated with 0.5, 2.5, 15.0, and 50 micrograms/kg had mean primary tumor diameters smaller than the control group. Evaluation of IL-12 therapy on primary tumor growth, mean diameters of primary tumors, survival rate, and development of lung metastases showed that the best results were observed using 300 ng/mouse (15 micrograms/kg) R mIL-12.

Animals↗