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Biomedical subjects

O Merimsky

Publications and source records attributed to O Merimsky.

At least 55 records · Page 3Linked to original sources
PubMed1998

Mononuclear cells release low molecular weight factors with anti-cancer activity: A lower level of production by cells of cancer patients.

Following the clinical observations that tumor metastases are extremely rare in striated muscles we defined recently a low molecular weight factor which is released by muscle cells (muscle factor, MF) and possesses specific anti-proliferative activity against tumor cells. we demonstrate that peripheral blood mononuclear cells constitutively release low molecular weight factor (LMF) similar to the MF which is capable of inhibiting in vitro the proliferation of carcinoma, melanoma, leukemia and lymphoma cell lines. The proliferation of normal cells such as bone marrow or fibroblasts was not inhibited but slightly stimulated following incubation with the LMF. Biochemical purification of this factor by several HPLC steps revealed that the inhibitory activity against tumor cells was concentrated within two definitive peaks. The LMF affects tumor cell growth by arresting them in the G0/G1 of the cell cycle and its activity is species and tumor non-specific. In vivo studies in melanoma- bearing mice revealed that the LMF inhibited melanoma growth when given either intraperitoneally or orally. Mononuclear cells from cancer patients with different malignancies (non-Hodgkin lymphoma, malignant melanoma, colon carcinoma and carcinoma of the rectum) secreted lower level of LMF in comparison to healthy subjects. The capability of the LMF to inhibit tumor cell growth and promote normal cell proliferation combined with its bioavailability in vivo may lead to its potential therapeutic and diagnostic use.

Animals↗
PubMed1997

Erotomania following an orchiectomy: a case report.

A case report of young male patient with erotomania following seminoma and orchiectomy is described in this article. The probable dynamics that lead to this delusion are then discussed. This case report demonstrates the cooperation between the oncology ward and the psychiatric liaison service.

Adult↗
PubMed1997

Palliative major amputation and quality of life in cancer patients.

Limb sparing surgery has replaced the amputation surgery in the treatment of limb sarcomas. Recurrent or persistent disease constitutes a major problem. Local symptoms such as agonizing pain, fractures, tumor fungation, inability to walk and inability to maintain daily activities, further impair the patient's quality of life. In this clinical set-up palliative amputation should be considered. Eighteen patients with soft-tissue or bone sarcomas and 3 patients with metastatic carcinoma underwent palliative major amputation. Hemipelvectomy was performed in 3 patients, hip disarticulation in 10, knee disarticulation or below-knee amputation in 3 patients, shoulder disarticulation in one patient and forequarter amputation in 4 patients. Local control of the disease and pain and improvement of the performance status were observed in 19 evaluable patients. The mobility was restored in 15 patients with lower limb surgery. The median survival following the procedure was 9 months. There was only one case of immediate post-operative death. Severe phantom pain was not reported by any of the patients. Quality of life was reported to be improved by two-thirds of the patients. To conclude, we have, found palliative major amputation surgery worth performing in low-performance status cancer patients with locally advanced disease.

Adolescent↗
PubMed1997

Detection of melanoma by monitoring the intracellular fluorescein fluorescence polarization changes in lymphocytes.

The effectiveness of detecting melanoma by measuring the intracellular fluorescein fluorescent polarization (IFFP) of patients' SCM (structuredness of the cytoplasmic matrix)-responding lymphocytes was examined. SCM-responding lymphocytes from 46 melanoma patients and 32 healthy volunteers were labeled with fluorescein diacetate and challenged with different stimuli, and the resulting polarization was determined. The polarizations (P) obtained upon stimulation with nothing (P-0), encephalitogenic factor (P-EF), phytohaemagglutinin (P-PHA), or melanoma antigen (P-MEL), and the ratios RR(ef) (P-EF/P-PHA) and RR(mel) (P-MEL/P-PHA) were lower for SCM-responding lymphocytes from the patients as a group than for those of the controls. The specificity and sensitivity of the IFFP tests (using cutoff values) to detect melanoma were 90.6 and 73.9%, respectively. The IFFP tests may facilitate the discrimination between melanoma patients and healthy subjects, and may be used in follow-up of patients with melanoma.

Algorithms↗
PubMed1997

Synergism of tumor necrosis factor-alpha and melphalan in systemic and regional administration: animal study.

Tumor necrosis factor (TNF) is a highly cytotoxic cytokine. However, due to its severe side effects, the only clinical situation allowing its administration in humans is isolated limb perfusion (ILP). Early studies have shown that TNF alone is of limited efficacy even at high doses via ILP, and that a chemotherapeutic agent needs to be added. The most commonly used drug in this setting is melphalan which is considered to be synergistic with TNF. However, since melphalan has not been commonly used in sarcoma, we believed that confirmation of its synergistic effect with TNF in an experimental sarcoma model could prove valuable for future drug choice. B16F10 melanoma and CT26 colon carcinoma cells were injected subcutaneously (s.c.) into mice, while GF fibrosarcoma cells were injected s.c. into the hindleg of Wistar rats. The animals were then divided into four treatment groups: TNF alone, melphalan alone, TNF and melphalan, and 0.9% NaCl controls. Mice were treated with intraperitoneal injections and rats by ILP. TNF dosage was 20 microgram for mice and 200 microgram for rats. Melphalan was given at 5-10 mg/kg for both mice and rats. Results showed synergism of TNF and melphalan in both modes of therapy. In the systemic administration groups (mice carrying B16F10 and CT26 tumors), tumors increased in size in all but the combined TNF-melphalan group. In the regional delivery groups (rats carrying GF sarcoma cells treated via ILP), there was a 16% decrease in tumor volume in rats treated with TNF alone, a 29% decrease in rats treated with melphalan, and a 75% decrease in the combined TNF-melphalan group. In conclusion, TNF and melphalan proved to be highly synergistic in both systemic and regional delivery. This fact makes melphalan an adequate choice for TNF perfusion in advanced limb malignancies.

Animals↗
PubMed1996

Palladium-103: a new radioactive source in the treatment of unresectable carcinoma of the pancreas: a phase I-II study.

Palladium-103 (Pd-103) is introduced in brachytherapy procedures because of its favorable physical properties, including its low energy, rapid dose fall-off, short half-life, and total cumulative dose delivery at a higher dose rate than iodine-125 (I-125) isotope. Intraoperative brachytherapy using I-125 pellets was reported to provide significant palliation and meaningful prolongation of life in highly selected patients with unresectable carcinoma of the pancreas. After considering some of the advantages of Pd-103 over I-125, we designed a phase I-II clinical trial to assess the feasibility of intraoperative Pd-103 in unresectable carcinoma of the pancreas to study the related morbidity when combined with chemotherapy and external beam radiation, and to evaluate the impact on palliation and local control rates. Between December 1989 and December 1993, 15 patients with biopsy-proven unresectable adenocarcinoma of the pancreas were treated with interstitial Pd-103 implants during laparotomy. In 13 patients the lesion was located in the head of the pancreas, in one patient in the uncinate process, and in one patient in the body of the pancreas. The stage distribution was as follows: T1 = 2; T2 = 6, and T3 = 7. In addition, all patients underwent biliary and gastric bypass. The mean number of Pd-103 pellets was 45; the mean total activity to obtain a matched peripheral dose (MPD) of 11,000 cGy was 68.9 mCi. The mean tumor volume encompassing the MPD was 16.5 cc. All patients received postoperative external beam radiation (4,500 cGy over 4 1/2 weeks) and chemotherapy (5-fluorouracil and mitomycin C). This combined treatment, consisting of intraoperative brachytherapy using Pd-103 and postoperative external beam radiation with chemotherapy, was well tolerated in all patients. These were no treatment-related mortalities, and no serious complications, such as bleeding or fistula formation. Pain relief was obtained within 3-6 weeks in 10 out of 12 patients presenting with pain. Survival ranged from 6 to 24 months (median 10 months). The study suggests that Pd-103 can be considered an alternative to I-125 for interstitial brachytherapy for unresectable carcinoma of the pancreas. Symptom relief appeared to occur faster and complications are significantly less. However, this study did not show any improvement in the median survival rate over I-125 due to the advanced stage cancer in the majority of patients in the study.

Adenocarcinoma↗
PubMed1996

Anti-tyrosinase antibodies in malignant melanoma.

Anti-tyrosinase antibodies were measured by enzyme-linked immunosorbent assay in sera of patients with malignant melanoma with either metastatic disease or no evidence of disease, in patients with melanoma and associated hypopigmentation (MAH), in patients with vitiligo and in healthy volunteers. The mean relative absorbance (Arel) was calculated by dividing the absorbance of each sample by the mean value for the control group. Using this method, the Arel of the control group was 1.000(SE 0.083). Arel of patients with metastatic disease (1.516; SE 0.225) was significantly higher (P = 0.03) than the value for the controls, but insignificantly higher than that for patients with no evidence of disease (1.216; SE 0.148). Patients with no evidence of disease, in whom the primary lesion originated in the lower limb, had a significantly higher (P = 0.01) Arel than the healthy volunteers. Patients with metastatic disease showed higher Arel if their primary lesions were confined to the area of the head and neck or to the lower limb. Patients with vitiligo had higher Arel values for their anti-tyrosinase antibody than any of the other groups. However, those with melanoma and MAH (vitiligo-like) had the same Arel of anti-tyrosinase antibodies as the controls or the patients with metastatic melanoma. This observation reflected the possible absorption of anti-tyrosinase antibodies to melanoma antigens, and pointed to the participation of anti-tyrosinase antibodies in the destruction of normal melanocytes in patients with melanoma, as part of the immune reaction towards this disease.

Adult↗
PubMed1996

Computed tomography features of cerebral spread of malignant melanoma.

The CT features of cerebral involvement by metastatic malignant melanoma are described in 28 patients. The most common locations of the primary lesion were the trunk and lower limbs. There was a high incidence of extracerebral metastasis at the time of diagnosis of cerebral involvement. Headache and behavioral changes were the most frequent presenting symptoms; 7% of patients with asymptomatic. The cerebral metastases were classified by size (< 1 cm, 1-4 cm, > 4 cm), with more than half measuring 1-4 cm. The larger lesions usually occurred singly. Peritumoral edema was detected in 89% of patients, hemorrhage in 19%, pressure signs on the ventricles in 37%, midline deviation in 15%, and leptomeningeal spread in 11%. No correlation was noted between size of tumor and other radiological features. Unilateral involvement was documented in 44% of cases. In the majority of patients the metastases were located at the periphery of the brain, mostly in the temporal and parietal lobes. Neuroimaging studies of the brain in asymptomatic patients with malignant melanoma may reveal occult metastases and influence the choice of treatment.

Adult↗
PubMed1996

Malignant melanoma of the head and neck. Clinical and immunological considerations.

Prolonged exposure to sun for long periods during most of the year has led to an increase in the frequency of malignant melanoma in Israel, especially for head and neck (H&N) melanoma. H & N melanoma is found in males more than in females and diagnosed when already locally advanced. The disease-free interval between treatment of the primary lesion and recurrence of the disease correlated with the patient's age and the depth of invasion according to Breslow. A higher recurrence rate correlated with male gender, location in the scalp, and the stage of the disease. Metastatic disease involved the lungs, liver, and brain and responded poorly to systemic therapy. Improved survival was related to female gender, early stage of the disease, low Breslow thickness, and location of the primary lesion elsewhere than the scalp. Immunologically, we found that the titers of antimelanoma antibodies in patients with metastatic disease originating in the area of the head and neck were higher than the titer in disease-free H & N melanoma patients (p = 0.05). Moreover, patients with metastatic H & N melanoma had a higher titer of antityrosinase antibodies compared with healthy subjects. These two types of antibodies might be used as markers for disease progression in H & N melanoma. The more aggressive character of H & N melanoma was not reflected by different titers of antimelanoma antibodies nor by antityrosinase antibodies in patients with H & N versus non-H & N melanoma.

Adult↗
PubMed1996

Melanoma-associated hypopigmentation: where are the antibodies?

Antibodies to the B16 melanoma cell line and to tyrosinase have been recently defined in our laboratory in sera of patients with vitiligo, melanoma, melanoma-associated hypopigmentation (MAH), and in healthy subjects. The antibody titers in each subject were measured by enzyme-linked immunosorbent assay, were compared with the mean optical density (OD) of the control group, and were expressed as relative OD. The titers of anti-B16 antibodies (relative OD +/- standard error) were 1.000 (0.058) in the controls, 1.025 (0.077) in patients with metastatic melanoma, 0.5862 (0.15) in MAH, 1.377 in surgery-induced MAH, 1.087 in vaccination with anti-idiotypic antibodies, and 2.098 (0.15) in autoimmune vitiligo. The titers in vitiligo were significantly higher (p < 0.0001) than in MAH or in healthy controls. Antityrosinase antibodies were found in titers of 1.000 (0.1024) in the controls, 1.516 (0.225) in metastatic melanoma, 1.027 (0.180) in MAH, 1.075 in surgery-induced MAH, 2.308 in vaccination-induced MAH, and 4.536 in vitiligo. Differences were found between vitiligo and MAH (p = 0.008), surgery-induced MAH (p = 0.009), vaccination-induced MAH (p = 0.059), and healthy subjects (p < 0.0001). The results of this study point to the cross-antigenicity between melanocytes and melanoma cells, and to participation of antibodies against melanoma-associated membrane antigens in the mechanism leading to the development of MAH in patients with melanoma.

Adult↗
PubMed1996

Tumor ploidy as a risk factor for disease recurrence and short survival in surgically treated Dukes' B2 colon cancer patients.

The risk factors for colon cancer recurrence following a curative intent surgery include the tumor location and size, the presence of adhesions, perforation, bowel obstruction, depth of invasion, histological grade, percentage of S phase content and cell kinetic profile. The DNA content of tumor cells has recently been suggested as an additional prognostic factor. In this study we assessed the tumor ploidy as a prognostic factor for recurrence and survival in colon cancer patients. The DNA content of colon cancers in 20 Dukes' B2 patients followed up at our center, who relapsed either locally or systemically, following surgical treatment was measured by image analysis. The data were pair-matched for age, sex, tumor site and grade, and the period of follow-up with 20 Dukes' B2 patients who had no evidence of disease. Aneuploidy occurred in 16 (80%) patients with recurrence, whereas only in 8 (40%) in the control group. Nonaneuploid DNA content was found in 12 (60%) patients of the control group, but in only 4 (20%) patients with a relapse. Aneuploidy was associated with a significantly higher tumor recurrence rate (p = 0.024) and shorter overall survival (p < 0.002). Our data point to a possible indication of a systemic adjuvant chemotherapy in Dukes' B2 colon cancer patients who have aneuploid tumors on image analysis. This should be further investigated in a prospective controlled randomized study.

Aged↗
PubMed1996

Detection of colon cancer by monitoring the intracellular fluorescein fluorescence polarization changes in lymphocytes.

Structuredness of the cytoplasmic matrix (SCM)-responding lymphocytes from healthy donors can be differentiated from SCM-responding lymphocytes of patients with malignant disease on the basis of the change in the intracellular fluorescein fluorescence polarization (IFFP) induced by their exposure to various antigens. We have found that the overall sensitivity, specificity and positive and negative predictive values of the test were 92.0, 92.6, 96.3, and 84.7%, respectively. We demonstrated the capability of the test to distinguish between healthy people and colorectal cancer patients per stage of the disease. We also found a significant difference in IFFP values between Dukes' C patients and patients with metastatic disease, rendering the test potentially helpful in follow-up.

Adult↗
PubMed1996

Reactivity to tyrosinase: expression in cancer (melanoma) and autoimmunity (vitiligo).

Anti-tyrosinase antibodies are found in the sera of patients with diffuse vitiligo, metastatic melanoma and in sera of patients with melanoma and hypopigmentation (MAH). The autoantigen is tyrosinase itself, the enzyme that participates in pigment (melanin) formation by both melanocytes and melanoma cells. The production of autoantibodies in both diseases is associated with the development of white patches on the patients' skin. The presence of these autoantibodies in patients with melanoma may suggest a better prognosis. Cross-antigenicity between melanoma cells and normal melanocytes is most probably the key mechanism leading to the appearance of MAH. Anti-tyrosinase antibodies are absorbed by melanocytes and by melanoma cells in all the 3 situations (melanoma, vitiligo, MAH). However, since the production of antibodies in vitiligo exceeds that in melanoma or MAH, the antibodies are detected in significantly higher levels only in vitiligo. It is suggested here that anti-tyrosinase antibodies may be responsible, or at least participate in destruction of normal melanocytes during the immune response to melanoma antigens. This mechanism may be responsible for the phenomenon of MAH in patients with melanoma, and for the formation of the autoimmune vitiligo. Anti-tyrosinase antibodies may serve for two clinical applications. One is a marker for monitoring and follow up of patients with melanoma treated by immune therapy. The second is active (or passive) immunotherapy. We have recently shown that C57BL/6J mice immunized with tyrosinase generated a high titer of antityrosinase antibodies, and following the inoculation of melanoma cells developed lower number of lung metastases, compared to the unvaccinated control group.

Autoantibodies↗