The treatment of melanoma with m-AMSA. A Cancer and Leukemia Group B phase II study

The activity of m-AMSA was evaluated IN 39 patients with advanced malignant melanoma. Seventy-nine percent of the patients had some prior chemotherapy. The others had some combination of surgery, radiotherapy, and immunotherapy prior to this study. Patients were treated every 3 weeks starting with 60 or 120 mg/m2 of m-AMSA depending on the extent of prior treatment. Doses were escalated if nadir WBC counts were greater than 2500/microliter. Leukopenia was the dose-limiting toxicity with 7.5% of patients having nadir WBC counts less than 1000/microliter. Of the 39 patients evaluable for response, all had progressive disease. In this study, m-AMSA in myelosuppressive doses was not active in malignant melanoma.     

Distribution of type IV collagen in benign and malignant epithelial proliferations. An indirect immunofluorescence study on the breasts, the lungs, and the skin

The distribution of type IV collagen in benign and malignant epithelial proliferations of the breasts, the lungs, and the skin was studied by an indirect immunofluorescence technique using specific antiserum. In benign lesions of the breasts, the staining for type IV collagen was present in all vascular and glandular basement membranes. In basal cell carcinoma of the skin, the basement membrane labeling was also found to be continuous. In malignant lesions of the breasts, the lungs, and the skin, staining for type IV collagen was seen only around well-differentiated glandular structures and in close contact to basal epidermal cells. This staining appeared as an irregular network. Of particular interest was the localization of type IV collagen in non-infiltrating lesions of the breasts and the bronchi where discontinuity in the basement membrane staining was observed. In contrast, there were no disruptions of basement membrane labeling in skin senile keratosis and in Bowen's disease. We conclude that the loss of type IV collagen seen in malignant proliferations in our study is related to overt or potential tumor cell infiltration and aggressiveness.     

Ultrastructural localization of voltage-sensitive sodium channels using [I]α scorpion toxin

The distribution of α scorpion toxin (α-ScTx) receptors was examined in differentiated mouse neuroblastoma cell cultures (N IE 115 clone) by electron microscope autoradiography using [¹²⁵I]α-ScTx. This neurotoxin binds specifically to voltage-sensitive sodium channels, slowing down the inactivation of the sodium permeability. Quantitative analysis demonstrated that only plasma membranes were labelled. The α-ScTx receptors seemed to be randomly dispersed on both cell bodies and cell processes. Microvilli protruding from the cell bodies carried more sodium channels than other parts of the membrane. The specific binding site density for α-ScTx varied from 4 (cell body membrane) to 13 (cell process membrane) per square micrometer.     

Multimodal approach to the treatment of stage III ovarian carcinoma: preliminary report of a pilot study and critical review

In an attempt to improve survival rates in Stage III, grade III-IV ovarian carcinoma (5 years survival rate less than 10%), we have tested the feasibility of a combined modality approach in 10 patients. Five of the 10 patients have been treated with surgery, chemotherapy, second look laparotomy, whole abdominopelvic irradiation and chemotherapy. Three patients are alive without evidence of disease (range 24 to 54 months) after entering the combined programme. We conclude that a combined modality therapy can be safely delivered. The acute toxic effects were not more frequent or more severe than with other therapeutic approaches. These results are compared with published reports in the literature.     

Olmsted syndrome--congenital palmoplantar and periorificial keratoderma

We are reporting the third case of the Olmsted syndrome, an entity that has received little attention in the medical literature. The syndrome consists of congenital diffuse, sharply marginated keratoderma of the palms and soles, onychodystrophy , constrictions of digits, and periorificial keratoses. Our patient, in addition, had congenital universal alopecia, absence of a premolar tooth, leukokeratosis of oral tissue, and hyperlaxity of the joints. The differential diagnosis includes hidrotic ectodermal dysplasia of the Clouston type, pachyonychia congenita, acrodermatitis enteropathica, keratoma hereditarium mutilans of Vohwinkel , mal de Meleda , and other forms of palmoplantar keratodermas . This patient had originally been reported as having acrodermatitis enteropathica, a condition with which the Olmsted syndrome can easily be confused.     

Androgens inhibit basal and estrogen-induced cell proliferation in the ZR-75-1 human breast cancer cell line

This study describes the inhibitory effect of 5 alpha-dihydrotestosterone (5 alpha-DHT) and its precursors testosterone (T) and androst-4-ene-3,17-dione (delta 4-DIONE) on the growth of the estrogen-sensitive human breast cancer cell line ZR-75-1. In the absence of estrogens, cell proliferation measured after a 12-day incubation period was 50-60% inhibited by maximal concentrations of 5 alpha-DHT, T, or delta 4-DIONE with half-maximal effects (IC50 values) observed at 0.10, 0.15 and 15 nM, respectively. This growth inhibition by androgens was due to an increase in generation time and a lowering of the saturation density of cell cultures. The antiestrogen LY156758 (300 nM) induced 25-30% inhibition of basal cell growth, its effect being additive to that of 5 alpha-DHT. The mitogenic effect of 1 nM estradiol (E2) was completely inhibited by increasing concentrations of 5 alpha-DHT with a potency (IC50 = 0.10 nM) similar to that measured when the androgen was used alone. E2 had a more rapid effect on cell proliferation than 5 alpha-DHT, the latter requiring at least 5 to 6 days to exert significant growth inhibition. As found in the absence of estrogens, maximal inhibition of cell proliferation in the presence of E2 was achieved by the combination of the antiestrogen and 5 alpha-DHT. Supraphysiological concentrations of E2 (up to 1 microM) were needed to completely reverse the growth inhibitory effect of a submaximal concentration of 5 alpha-DHT (1 nM). The antiproliferative effect of androgens was competitively reversed by the antiandrogen hydroxyflutamide, thus indicating an androgen receptor-mediated mechanism. The present data suggest the potential benefits of an androgen-antiestrogen combination therapy in the endocrine management of breast cancer.     

History of laparoscopic surgery.

Since the beginning of the 20th century physicians have promoted laparoscopy as a valuable adjunct to the diagnosis of diseases of the abdominal cavity. Laparoscopy, however, failed to become popular among abdominal surgeons until the advent of laparoscopic cholecystectomy. This single new operative approach to the treatment of gallbladder stones gave rise to such enthusiasm among general surgeons that other innovative laparoscopic procedures are now being promoted in ever-increasing numbers. The general surgeon has again become the leader in the introduction of a new surgical approach. This new technique must be developed with great care, and there must be rigorous criteria for its use, critical analysis of the technique and honest reporting of results.