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Biomedical subjects

O Merimsky

Publications and source records attributed to O Merimsky.

At least 73 records · Page 4Linked to original sources
PubMed1995

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 presence of metastatic disease, the tumor location and size, number of positive lymph nodes, 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 colon cancers in 20 Dukes' B2 patients in follow-up evaluation 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 with 20 Dukes' B2 patients who had no evidence of disease. Aneuploidy occurred in 16 (80%) patients with recurrence, as compared with only in 8 (40%) in the control group. Aneuploidy was associated with significantly higher tumor recurrence rate (P = 0.024) and shorter overall survival (P < 0.002). Our data may point out a possible indication for systemic adjuvant chemotherapy in Dukes' B2 colon cancer patients who have aneuploid tumors on image analysis. This warrants further investigation in a prospective controlled randomized study.

Adult↗
PubMed1995

Carboplatin-related idiosyncrasy.

Side effects of cisplatin and carboplatin include nausea, vomiting, peripheral neuropathy, nephrotoxicity, hearing loss, bone marrow depression, and rarely Lhermitte's sign and allergic reactions. A unique case of idiosyncrasy related to carboplatin administration was observed in a young woman treated for ovarian cancer. Symptoms and signs included skin rash, shortness of breath, and redness of face and upper trunk, without drop in blood pressure or change in heart rate, and were resolved within a short time following administration of hydrocortisone and promethazine.

Adenocarcinoma↗
PubMed1995

Anti-tyrosinase antibodies participate in the immune response to vaccination with anti-idiotypic antibodies mimicking the high-molecular-weight melanoma-associated antigen.

Seven patients with metastatic melanoma were vaccinated with anti-idiotypic monoclonal antibody (mAb) MK2-23 which mimics the high-molecular-weight melanoma-associated antigen (HMW MAA). Sera samples were assayed for anti-anti-idiotypic antibodies, by Ab1-Ab2 complex inhibition test, for anti-B16 epitope antibodies, which are a heterogeneous group against various antigens presented on B16 melanoma cells and for anti-tyrosinase antibodies, which are specific against tyrosinase. Our results pointed to the participation of anti-tyrosinase antibodies in the immune response to vaccination by anti-idiotypic antibodies mimicking the HMW MAA. The anti-tyrosinase antibody kinetic curves presented an initial increase in titres in five cases followed by decreasing titres; in two cases a constant decrease was noted. The inhibition assay demonstrated an increasing percentage of inhibition (range 17-100%) within 100-400 days of treatment. The titre of the anti-tyrosinase antibodies increased following the vaccination, then decreased--probably due to absorption of the antibodies to melanoma cells and normal melanocytes. A positive slope in the percentage of inhibition was roughly associated with a negative slope of anti-tyrosinase antibodies. In one case, a long-standing complete clinical response was accompanied by development of melanoma-associated hypopigmentation. Anti-B16 epitope antibodies had no role in the response to vaccination. The development of anti-tyrosinase antibodies in response to vaccination by anti-idiotypic antibodies mimicking another antigen may be explained by induction of non-specific polyclonal B lymphocytes activation, a well-recognized phenomenon in autoimmune disorders.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Anti-Idiotypic↗
PubMed1995

A phase II trial of D-Trp-6-LHRH (decapeptyl) in pretreated patients with advanced epithelial ovarian cancer.

Fourteen patients with advanced ovarian cancer who failed chemotherapy received a long-acting LHRH agonist. All the patients had been previously operated on and all had received at least one regimen of chemotherapy. Duration of decapeptyl administration was between 1 month and 28 weeks. There were no complete or partial responses. Eight patients (57%) had disease stabilization with a median progression-free interval of 14 weeks (range 4-28 weeks). All other patients developed a clear progressive cancer after the first injection of LHRH agonist. Three of these patients are still alive and receiving other forms of chemotherapy (median follow-up after the end of LHRH treatment was 11.5 months). The regimen was well tolerated with only mild toxicity observed (hot flushes in 2 patients). Although D-Trp-6-LHRH (Decapeptyl) was well tolerated, it had insignificant activity in treating patients with epithelial cancer that was resistant or relapsed after first-line platinum-based chemotherapy.

Aged↗
PubMed1994

Postoperative high dose-rate intravaginal brachytherapy combined with external irradiation for early stage endometrial cancer: a long-term follow-up.

PURPOSE: To evaluate the long-term control of disease and cure rate, complications, second malignancy, and survival of early-stage endometrial cancer patients treated with surgery, high dose-rate brachytherapy, and external beam radiation therapy. METHODS AND MATERIALS: From 1969 through 1979, 300 patients with clinically staged Stage I-II endometrial cancer underwent total abdominal hysterectomy and bilateral salpingo-oopherectomy, followed by high dose-rate intravaginal radiation, 7 Gy x 3 to 0.5 cm from the mucosal surface, using a remote afterloading technique. External beam radiation therapy, 40 Gy to midplane in 4 weeks, was delivered to high risk patients through AP/PA and lateral fields. RESULTS: The patients were followed for 5-24 years (median 12). The actuarial progression-free survival rate was 96.6%. Post-treatment grade 1-2 actuarial complication rate was 9.5%, including cystitis (4.5%), vaginal stenosis (2.5%), proctitis (1.5%), vaginal necrosis (0.5%), and partial bowel obstruction (0.5%). Neither grade 3-4 complications nor additional late complications were observed in any of our patients. Relapse rate was only 3.7%, of which 45.5% were local, 45.5% were distant, and 9% were mixed. All the patients with relapse were postmenopausal, age range of 58-77 years, with tumor grade 2-3 in 64%. Second primary cancer rate was 12.8% (mostly breast and colon). Factors that were associated with improved prognosis were young age, premenopausal, low grade, no extrauterine disease, and a histology of adenocarcinoma (adenocarcinoma with squamous metaplasia). CONCLUSION: High dose rate intravaginal radiation therapy combined with surgery and external beam radiation therapy achieved a high cure rate small number of minor complications. No long-term treatment-related complications were noted in any of the patients. This treatment combination may be safely applied to patients with early stage endometrial cancer.

Adult↗
PubMed1994

Treatment of disease-negative but mucin-like carcinoma-associated antigen-positive breast cancer patients with tamoxifen: preliminary results of a prospective controlled randomized trial.

Increasing levels of tumor markers such as carcinoembryonic antigen, mucin-like carcinoma-associated antigen (MCA), CA 15.3, and monoclonal antibody H23 in breast cancer patients following the treatment of the primary disease and adjuvant radiation and chemotherapy reflect subclinical development of metastatic disease. Overt metastatic disease is usually incurable and prolongation of life at this stage is impossible, and the treatment is only palliative. The efficacy of tamoxifen, a least-toxic agent, in the treatment of early and minimal metastatic disease detected only by increasing serum levels of MCA was studied prospectively in a randomized study. Our preliminary, albeit encouraging, results showed that the rate of relapse within a median follow-up period of 11 months was 24.1% in the control arm as compared with 0% in the tamoxifen arm (Fisher's exact test, P = 0.012). None of the patients with a relapse had positive progesterone receptors (PR). We may carefully conclude that early treatment may be warranted in young patients with negative PR and continuously increasing serum levels of the marker.

Adult↗
PubMed1994

Vitiligo- and melanoma-associated hypopigmentation: a similar appearance but a different mechanism.

The significance of the association between the appearance of hypopigmentation in patients with melanoma and the prognosis is still not clear. It was postulated that, in melanoma, an immune response is responsible for the destruction of the malignant as well as the normal pigmented cells, and that the eventual development of vitiligo-like patches in melanoma patients improves their prognosis. We studied the level of anti-melanoma antibodies in the sera of patients with melanoma with hypopigmentation and compared it to the titer in patients with melanoma only, to the titer of patients with vitiligo, and to that of healthy subjects. Only IgG-type antibodies were found in the sera of patients with vitiligo, with melanoma, or with melanoma with hypopigmentation. No significant differences in the titer of anti-melanoma antibodies could be found between the patients with melanoma when subgrouped according to the initial stage and the status of the disease at the time when the test was carried out. Statistically significantly (P < 0.001) higher titers of antibodies were detected in the sera of patients with vitiligo in comparison to the lower titers in the other groups. Our results point to a similar immunobiological status, which probably does not give any advantage to patients with melanoma with hypopigmentation compared to patients without it. The appearance of hypopigmentary plaques in melanoma patients should be regarded, in our opinion, as a concomitant immunological phenomenon of the disease.

Adolescent↗
PubMed1994

Chemotherapy-related persistent indirect hyperbilirubinemia.

In spite of the improvement on chemotherapy results in treating testicular cancer and the introduction of adjuvant chemotherapy to node negative (as well as node positive) breast cancer patients, there is still present a wide spectrum of early and late toxic manifestations. The combination of cisplatin, vinblastine and bleomycin given to testicular cancer might result in cariovascular, neurological, gastrointestinal and renal problems. Late effects of cyclophosphamide, methotrexate and 5-fluorouracil given to breast cancer patients might cause obesity, amenorrhea and infertility. We report a persistent asymptomatic indirect hyperbilirubinemia which was observed in two cancer patients (breast; testis) 3 and 14 months following the cessation of chemotherapy. Metastatic liver disease and involvement of other sites, as well as other causes of hyperbilirubinemia, were excluded. The exact cause of the indirect hyperbilirubinemia remained obscure.

Adult↗
PubMed1994

Antigens and antibodies in malignant melanoma.

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.

Animals↗
PubMed1993

Sphenoid and cavernous sinuses involvement as first site of metastasis from a fallopian tube carcinoma. Case report.

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.

Aged↗
PubMed1993

Recombinant interferon alpha-2a in combination with dacarbazine in the treatment of metastatic malignant melanoma: analysis of long-term responding patients.

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).

Adult↗
PubMed1993

Effect of allogeneic tumor cells, interleukin-2 and interleukin-6, on the growth of subcutaneous syngeneic tumors.

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.

Animals↗
PubMed1993

Cisplatin and doxorubicin for invasive basal cell carcinoma of the eyelids.

Cisplatin and doxorubicin were used in the treatment of recurrent invasive basal cell carcinoma (BCC) of the medial canthus and orbit. Complete remission was observed after treatment termination, and this was still evident five years later. Systemic chemotherapy offers an alternative mode of treatment for selected cases of advanced BCC.

Aged↗
PubMed1992

Kaposi's sarcoma on a lymphedematous arm following radical mastectomy.

Chronic lymphedema predisposes for local immune incompetence, manifested by development of Stuart-Treves syndrome, Kaposi's sarcoma and fibroma-like lesions. A 91-year-old female with multiple cancers developed classic Kaposi's sarcoma on a chronically lymphedematous arm 26 years after radical mastectomy and irradiation of the involved axilla. The Kaposi lesion partially responded to electron beam irradiation.

Aged↗
PubMed1992

Brain metastases of malignant melanoma in interferon complete responders: clinical and radiological observations.

Three patients with metastatic malignant melanoma, 2 of whom were males with primary lesion on the shoulder, and a female with primary lesion on the ankle, with Clark's level III-IV, completely responded to interferon-DTIC, but failed in the brain. Radiologically, all the lesions were peripheral in location, and none showed any bleeding tendency. Clinically, these lesions seemed to be resistant to radiotherapy, chemotherapy or steroid treatment, and were the cause of death after a very short survival period. Interferon apparently is inactive against melanoma brain metastases, but does cause CNS symptoms. Because CNS metastases are sometimes the sole site of clinical relapse, and are frequently disabling, prophylactic cranial irradiation (PCI) needs to be studied in high risk patients.

Aged↗
PubMed1992

Interferon-related cortical blindness.

The term cortical blindness indicates loss of sight due to bilateral lesions in the occipital lobes. It is a rare but severe side effect produced by chemotherapeutic agents. Cortical blindness was diagnosed in a 75-year-old man who had been treated with alpha-interferon for metastatic renal-cell carcinoma. The absence of focal neurological signs and of abnormal findings as determined by two repeated computed tomography (CT) scans of the brain, which excluded structural damage to the occipital lobes, suggest that metabolic or toxic reactions may have caused the cortical blindness diagnosed in our patient. The temporal relationship between the treatment with alpha-interferon and the development of cortical blindness indicates that this substance may have been the causative agent for this phenomenon.

Aged↗
PubMed1992

Fotemustine and DTIC combination in patients with disseminated malignant melanoma.

Seventeen patients with histologically proven melanoma and measurable metastatic disease received 7-week cycles of fotemustine 100 mg/m2/day on days 1 and 8, and decarbazine (DTIC) 500 mg/m2/day on days 15 and 16, in a prospective open study, to assess the efficacy of fotemustine-DTIC combination. Response rate was 11.7%: one partial response (PR) in brain for 4.5 months, and one PR in brain and lymph nodes for 4 months. There was also one (5.8%) minimal response (MR) in brain, stomach, and lymph nodes for 8 months, and three (17.6%) patients with stable disease. Survival of responders was significantly superior to nonresponders. There was no response in brain without response in extracerebral sites. Toxicity was generally mild and well tolerated by all the patients. Fotemustine-DTIC showed some activity against metastatic melanoma, and should be further evaluated.

Adult↗