Conjunctival involvement in classic (indolent) HIV negative Kaposi's sarcoma.
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Biomedical subjects
Publications and source records attributed to S Chaitchik.
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Antigens, antibodies and immune complexes seem to play a major role in the course of malignant melanoma, in detection of the disease progression, in treatment planning and monitoring. Of particular interest are cell and matrix adhesion molecules, growth factors and cytokines, proteases, gangliosides and major histocompatibility complex class I and II molecules. Antigens expressed on melanoma cells, but not on mature melanocytes, may be used as markers for the degree of the differentiation of the melanoma cells. The more the melanoma cells are dedifferentiated, the smaller is the antigenic similarity to normal melanocytes. Also, different antigens may be identified in various stages of the disease and may be used as tumor markers for disease recurrence or progression. Certain melanoma-associated antigens (MAA) such as epidermal growth factor receptor and adhesium molecules can be modulated by cytokines. Early melanoma evokes an antigen-derived T cell response, which becomes attenuated with the progression of the disease. A variety of cell adhesion molecules present on melanoma cell surfaces may play a role in regulation of cellular cytotoxicity. Free antimelanoma antibodies are usually not detectable in the sera of patients with melanoma, possibly due to their binding to shed antigens and formation of immune complexes or to tissue antigens. When bound to normal melanocytes, they cause the appearance of associated hypopigmentation. The identification of melanoma surface antigens led to generation of monoclonal antimelanoma antibodies (MAb) by laboratories. Strategies utilizing MAb based on immunologic approaches have been developed. MAb to tumor-associated antigens of melanoma cells may be used for therapeutic purposes in man. Sera of patients with vitiligo were capable of causing regression of melanoma metastases in mice due to the presence of a high titer of naturally occurring antimelanoma antibodies. Immunization of melanoma patients with vaccines containing treated melanoma cells or specific melanoma antigens or anti-idiotypic antibodies resulted in an increasing titer of antimelanoma antibodies and regression of the tumor to some extent. The appearance of hypopigmentation in patients with melanoma serves as proof for the activity of antimelanoma antibodies, although its association with the prognosis is still not clear. The thorough investigation in the field of MAA and related antibodies is aimed at improving specific antimelanoma immunotherapy, such as antigenic targeting or enhancement of production of autoantibodies, as well as better understanding of the process of metastasis and the melanoma-immune system interaction.
The prognostic value of serum CA-125 levels both before chemotherapy and after each cycle of one or two courses was assessed in 48 patients with advanced ovarian adenocarcinoma. All patients received a minimum of six courses of either cyclophosphamide and cisplatinum (CP) or cyclophosphamide, doxorubicin and cisplatinum (CAP). Patients with serum CA-125 values below the normal value of 35 U/ml after two courses had a significantly longer median survival (p < 0.0001) and longer disease-free survival (p = 0.007) than did those patients whose CA-125 levels dropped to normal after the third or a later course of chemotherapy. A response in CA-125 levels after the first two courses of chemotherapy may indicate which patients should continue with the current chemotherapy regimen and which patients should be offered salvage therapy.
The occurrence of central nervous system metastases in ovarian cancer patients ranges from 0.88 to 4.5%. Centra nervous system involvement in a fallopian tube carcinoma is extremely rare. A 77-year-old woman with an invasive tubal carcinoma was admitted because of ophthalmoplegia, sparing the lateral rectus muscle of the left eye, a decreased left corneal reflex and hypoesthesia along the distribution of the ophthalmic and maxillary branches of the left trigeminal nerve. CT scan showed a space occupying lesion in the left sphenoid sinus invading the left cavernous sinus and the submucosa of the left lateral wall of the nasopharynx, proven histologically to be a metastasis from her primary cancer. Attention should be paid to the possibility of distant and unusual metastases associated with tubal cancer in order to treat the patients promptly.
BACKGROUND: Vitiligo is a dermatologic disease characterized by local, dispersed, or diffuse white patches on the skin. The disease is defined as an autoimmune disorder because autoantibodies against membranal components of melanocytes are found in the patients' sera. The current study examined whether the autoantibodies reacting with the normal melanocytes could be a potent therapy against melanoma cells. METHODS: The three in vitro assays used to determine the antibody reactivities using a mouse melanoma cell line B-16-F10 and M-14 human melanoma cells as targets are as follows: enzyme-linked immunosorbent assay (ELISA), proliferation assay, and morphologic examination in the presence of antibodies purified from sera of patients with vitiligo. In the in vivo studies, experimental melanoma was intravenously induced in C57BL/6J mice, and the mice were treated by daily intraperitoneal injections with purified immunoglobulin G (IgG) fraction derived either from patients with vitiligo or from healthy subjects. RESULTS: The binding of IgG derived from patients with vitiligo was demonstrated by ELISA: Exposure of melanoma cells to the vitiligo autoantibodies was followed by inhibition of their proliferation capacity. In addition, morphologic alterations exemplified by detachment of the cells from their solid support associated with melanin release were observed in the B-16-F10 cells. Less metastatic foci developed in the lungs of the mice treated with the purified IgG fraction from the sera of patients with vitiligo compared with those treated with purified IgG fraction from healthy subjects. CONCLUSIONS: The results of this study point to the presence of anti-melanoma autoantibodies in the sera of patients with localized and diffuse vitiligo. These antibodies have a destructive effect on melanoma cells in vitro and in vivo.
In chemofiltration a large dose of a cytotoxic drug is infused into an artery supplying a cancerous area, thus limiting systemic toxicity. The venous return from the area is pumped into a chemofiltration unit at 750 ml/min and the drug is filtered out of the blood, which is then returned to the systemic circulation. Of 22 patients with locally advanced cancer, systemic chemotherapy had failed in 63%. 9 of them underwent chemofiltration of the liver for advanced metastatic cancer of the colon (4 cases), rectum (2), breast (2) and ovaries (1); and 13 underwent chemofiltration of the pelvis for advanced cancer of the rectum (5), malignant melanoma (5), ovaries (1), cervix uteri (1) and vulva (1). The following drugs were used: 5-FU (750 mg/m2/10 min) and mitomycin-C (30 mg/m2/10 min) for colorectal, ovarian and breast carcinomas; melphelan (1 mg/kg/20 min) or cisplatinum (200 mg/m2/30 min) for malignant melanoma or ovarian carcinoma; mitomycin-C or bleomycin (50 mg/m2/10 min) for carcinoma of the cervix or vulva. 1 patient with extensive liver metastases died of respiratory failure 28 days after the procedure. Surgically related complications occurred in 16% and included wound hematoma (2 cases), infection (1) and venous thrombosis (1). Drug-related complications occurred in 50%, and included transient leukopenia (9), mild renal failure (1), hair loss (2) and prolonged paralytic ileus (1). Partial remission was observed in 10/20 patients who had measurable disease. Time to progression was 5.4 months (range: 4 weeks to 20 months). Stabilization of disease occurred in 7/20 (35%), while in 3 the disease progressed.(ABSTRACT TRUNCATED AT 250 WORDS)
BACKGROUND: The Jewish population of Israel is divided into two ethnic groups: Ashkenazic Jews (AJ) who immigrated from Europe and are fair-skinned, and Sephardic Jews (SJ) who immigrated from the Orient and Africa and who are dark-skinned. The biologic behavior of malignant melanoma (MM) in these two groups has not been investigated. METHODS: Three hundred forty-eight of 380 patients with MM, who could be accurately grouped ethnically, constitute this study group. The gender, site and depth of primary tumor, metastatic involvement and survival analysis, including univariate analysis for level of invasion, were examined. RESULTS: Of 348 patients with MM, 285 were AJ and 63 were SJ. The female:male ratio was 2:1 and 0.9:1, for AJ and SJ, respectively (P < 0.05). Lesion site distribution was similar. The lesions were more invasive in SJ, 53% Clark level 4-5 versus 41% in AJ (P < 0.05). The 5-year survival was worse in SJ relative to AJ--50% versus 71% for female patients and 30% versus 62% for male patients--but did not reach statistical significance (NS). The actuarial 10-year survival showed poorer survival for female SJ: 27% versus 67% in female AJ (P < 0.05) and male SJ; 32% versus 65% in male AJ (P < 0.01). For all stage I MM, the actuarial 10-year survival was in male patients 32% versus 79% (P < 0.05), and in female patients, 27% versus 72% (P < 0.05) in SJ and AJ, respectively. For the more invasive lesions (Clark levels 4 and 5), the actuarial 10-year survival was for male patients 19% versus 75% (P < 0.05) and for female patients, 65% versus 67% (NS) in SJ and AJ, respectively. CONCLUSIONS: The dark-skinned SJ tend to have MM less than the fair-skinned AJ, but once MM occurs in SJ, it appears to have a more virulent nature.
Thirty-four evaluable patients with metastatic malignant melanoma were entered into a phase-II study designed to assess the response rate and analyze the long-term therapeutic efficacy of recombinant interferon (rIFN) alpha-2a and dacarbazine. Patients received 14 days of daily subcutaneous r-IFN alpha-2a (3 x 10(6) IU/day), followed by 9 x 10(6) IU on alternate days, as long as objective response lasted, in combination with i.v. dacarbazine started on day 7 (400 mg/m2) and repeated every 21 days (dacarbazine doses were escalated to 800 mg/m2). In 11 patients, 6 complete (17.6%) and 5 partial (14.7%) responses were seen, with an overall response rate of 32.3% (95% confidence interval: 16%-48%). The median survival time of the responding patients was significantly better than that of patients with progressive disease (P = 0.01) and the median response time of the patients showing complete response was longer than that of the partially responding patients (14 and 7 months respectively, P = 0.06).
In the present study we demonstrate the ability of allogeneic M3 tumor cells to induce an antitumor response against the syngeneic tumor, when injected locally together with syngeneic B16 melanoma cells. The replacement of the allogeneic tumor cells with either syngeneic or allogeneic splenocytes had no effect on the growth of the syngeneic tumor. Systemic administration of both interleukin-2 (IL-2) and IL-6 did not affect the antitumor response induced by allogeneic tumor cells. When mice, previously injected with B16 and M3 cells, were rechallenged subcutaneously with B16 tumor cells at a different anatomical site, an inhibitory effect in some, but not all, experiments was observed. Systemic injections of either IL-2 or IL-6 did not alter the antitumor effects of the allogeneic and syngeneic tumor-cell mixtures. The significance of our results in developing immunotherapy modalities based on active immunization with allogeneic tumor cells and selected cytokines is discussed.
In the present study we tested the phenotypic profile as well as several immunological responses of peripheral blood mononuclear cells (PBMC) isolated from melanoma patients. These patients underwent chemotherapy with dacarbazine and carboplatin from day 1 to day 22, followed by immunotherapy of low-dose recombinant interleukin-2 and recombinant interferon alpha administered subcutaneously from day 36 to day 75. The PBMC from 14 patients were isolated on day 0 before chemotherapy, on day 36 after chemotherapy and on day 76 after immunotherapy. After chemotherapy, a decrease in CD16+ cells and increase in CD3+ and CD4+ cells correlated with a significant decrease in the generation of lymphokine-activated killer (LAK) activity. After immunotherapy, an increase in CD16+ cells correlated with an increase in the induction of LAK activity. A comparison between responding and non-responding patients revealed statistically significant differences in LAK activity of PBMC and response to concanavalin A following chemotherapy, and in the percentage of CD8+ cells following immunotherapy. Our results point toward the value of continuing such a study on a larger population of cancer patients in order to select the appropriate bioassays for monitoring and predicting the clinical responsiveness to combined therapies.
In the present study we evaluate the antitumor efficacy of a glycosylated molecule of interleukin-6 (IL-6), which was cloned and expressed in Chinese hamster ovary cells. When tested with two syngeneic murine tumors, the MC38 adenocarcinoma and the MCA106 fibrosarcoma, recombinant IL-6 (rIL-6) significantly reduced the number of day-3 established MC38 lung metastases, but had no effect on MCA106 lung metastases. A similar effect of rIL-6 was seen on day-3 MC38 liver metastases. The antitumor activity mediated by rIL-6 was achieved at doses of the cytokine ranging from 6 micrograms to 150 micrograms/day. There was no correlation between the responsiveness to rIL-6 of these two tumors and their susceptibility, in vitro, to a direct cytostatic effect of the cytokine or the increase in the expression of major histocompatibility complex (MHC) antigens after exposure to rIL-6. However, a correlation was seen between the antitumor response to rIL-6 and the initial number of tumor cells expressing MHC antigens. The possible role of MHC antigens expressed on tumor cells, the generation of MHC-restricted cytotoxic cells and the responsiveness to IL-6 are discussed.
Life satisfaction (LS) is one of a set of constructs defining quality of life. Previous studies showed that LS was sometimes related to health and sometimes not. The study was designed to examine the relation of LS as a general construct to satisfaction in specific domains. We assumed that there is a tendency to maintain an acceptable level of LS even under stressful and threatening conditions, that it is related to optimism and that the likelihood of attaining satisfaction in a particular domain affected the selection of domains on which LS is based. We expected that in cancer patients LS would be related to more domains but not to health. The study was done with 55 head-and-neck cancer patients, of all stages and grades of tumor; 51 orthopedic patients, victims of accidents with good recovery chances; and 55 healthy individuals. The healthy individuals and orthopedic patients were matched (in terms of group values) to the cancer patients in age, gender and education. Single-item measures of LS and optimism, and a questionnaire with 49 multiple-choice items assessing adjustment in 13 domains were administered to all subjects. The results showed that in cancer patients LS was related to most domains but not to health and not to optimism, whereas in the other groups it was related to few domains including health, and also to optimism. The findings support the tendency to maintain LS with the materials available to the individual, and show that health is related to LS only if its maintenance or attainment are realistic goals. Thus, both bottom-up and top-down theories of LS are supported.
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Kaposi's sarcoma is a rare neoplasm of characteristic chronicity. The classical form which occurs most often in elderly men of Eastern European origin, comprises both an indolent, cutaneous type marked by spontaneous regression with prolonged survival, and a rarer, disseminated variant is more fulminant. Seven elderly Jewish patients with classical, disseminated, visceral Kaposi's sarcoma were studied; they were neither homosexual nor drug-abusers. All immunologic parameters were normal and serum tests for HIV antibodies, CMV, and EBV were negative. Five of these patients were treated and four responded well, including two complete remissions. The prolonged survival of these patients (82% at 5 years) suggests the existence of an indolent subtype or forme fruste of the usually aggressive form of classical Kaposi's sarcoma.
BACKGROUND: Little is known about the psychosocial effects of cancer survivors especially after the first stage of adjustment. The study was designed to provide information about the major psychological problems of head-and-neck cancer patients and their change with time since diagnosis. PATIENTS AND METHODS: The subjects were 55 head-and-neck cancer patients, 40 men and 15 women with disease stages I to IV, grade of tumors G1 to G3-4, and disease duration in the range of 3 months to 21 years. A questionnaire with multiple-choice and open-ended questions assessing adjustment in 14 domains (e.g., fears and worries concerning health, functioning in the family) was administered to patients and their partners or closest relatives as well as scales assessing anxiety, anger and depression. RESULTS: The results showed that the domains that were most problem-laden included coping with health problems, fears, communication with the partner and social relations. Comparing the problems of patients in different time periods (0.5-1.5 years after diagnosis, 1.5-5 years, and over 5 years) showed that many medical problems decreased with time but most psychological ones including anxiety and anger deteriorated markedly. CONCLUSIONS: Head-and-neck cancer patients suffer from a broad range of psychosocial problems that become exacerbated with time. The deterioration in quality of life may reflect 'patient burnout' which could be decreased by acquiring adequate coping skills.
Between 1982 and 1987, 43 patients with epithelial ovarian carcinoma, identified as International Federation of Gynaecology and Obstetrics Stages I-IV, underwent second-look laparotomy as a part of their treatment protocol. Twenty-nine patients (67%) had no evidence of residual disease, five (11.6%) had residual disease < or = 1 cm, and nine patients (20%) had residual disease > or = 1 cm at re-exploration. Persistent disease at the second operation was positively correlated with the initial clinical stage, and negatively correlated with the extent of the original cytoreductive surgery. Fifteen of 29 patients with negative findings (52%) developed recurrent disease within two years. All recurrences were limited to the abdominal cavity only. Three and five years survival, for the patients with negative findings, was 62% and 48% respectively. No documented benefit to the patients could be demonstrated by adopting second-look laparotomy as a routine procedure in the management of patients with epithelial ovarian carcinoma. In view of our data, as well as that of others, such operations cannot be considered a valuable routine procedure. At this point, second-look laparotomy may have a role in evaluating the efficacy of a post-surgical new chemotherapy treatment regimen.
Primary spinal epidural lymphoma (Stage I) is diagnosed predominantly late after a long prodromal phase of local back pain resulting in spinal cord compression. The use of CT and NMR images in the early stage of investigation and their analysis may help to diagnose these cases prior to the appearance of neurologic deficit. We report on 2 patients who presented with prolonged localized back pain with sudden symptoms of spinal cord compression. CAT scan and NMR imaging demonstrated the characteristic appearance of lymphoma. Decompressive laminectomy supported the diagnosis. Radiotherapy treatment to the region of the non-Hodgkin's lymphoma resulted in complete resolution. Thereafter, systemic chemotherapy with CHOP achieved a good response.