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Biomedical subjects

Ofer Merimsky

Publications and source records attributed to Ofer Merimsky.

At least 19 recordsLinked to original sources
PubMed2006

The role of imatinib mesylate (Glivec) for treatment of patients with malignant endocrine tumors positive for c-kit or PDGF-R.

Imatinib mesylate (IM), a small molecule that is a selective inhibitor of the ABL, platelet derived growth factor receptor (PDGFR-R) and stem cell ligand receptor (c-kit) tyrosine kinases (TK). IM was also found to inhibit the TK activity of BCR/ABL fusion protein produced in chronic myelogenous leukemia, with marked clinical activity against the disease. Since both PDGF-R and c-kit both having a putative role in tumorigenesis, we investigated the efficacy and safety of the use of IM in patients with endocrine tumors unresponsive to conventional therapies that expressed c-kit and/or PDGF-R (within the framework of a comprehensive phase II multi-center study of IM in patients with solid tumors). IM was initiated at a dose of 400 mg/day, with possible dose escalation within 1 week to 600 mg/day and an option to raise the dose to 800 mg/day in the event of progression and in the absence of safety concerns for a period of up to 12 months. Between September 2002 and July 2003, 15 adult patients with disseminated endocrine tumors were recruited as follows: medullary thyroid carcinoma (MTC, n = 6); adrenocortical carcinoma (ACC, n = 4); malignant pheochromocytoma (pheo, n = 2); carcinoid (non-secreting, n = 2), neuroendocrine tumor (NET, n = 1). No objective responses were observed. MTC--disease progression in 4 patients, and treatment discontinuation in 2 patients due to adverse events; ACC--disease progression in 3 patients, and treatment discontinuation in 1 patient due to severe psychiatric adverse event; Pheo--disease progression in 2 patients; Carcinoid--stable disease in 1 patient (6.5 months), and disease progression in 1 patient; NET--disease progression in 1 patient. IM does not appear to be useful for treatment of malignant endocrine tumors, also causing significant toxicity in this patient population.

Adolescent↗
PubMed2005

Limb sparing approach: adjuvant radiation therapy in adults with intermediate or high-grade limb soft tissue sarcoma.

BACKGROUND: Limb soft tissue sarcomas (STS) are currently treated with limb sparing surgery (LSS) followed by radiation therapy (RT). PATIENTS AND METHODS: Between October 1994 and October 2002, 133 adult patients with intermediate or high-grade limb STS were approached by LSS+RT. RESULTS: RT related toxicity was manageable, with a low rate of severe effects. At 4-year median follow-up, there were 48 recurrences of any type, 23 of isolated local failure, and 35 of systemic spread w/o local failure. DFS and OS were influenced by disease stage II vs I, primary site in the upper limb vs lower limb, MPNST vs other types, induction therapy vs no induction, adequate resection vs marginal resection or involved margins, and good response to induction therapy vs bad response. DFS and OS were Patient's age and sex, tumor depth, acute or late toxicity of RT, or the interval of time between the date of definitive surgery and the start of RT did not affect DFS and or OS. CONCLUSIONS: The RT protocol is applicable in the era of complicated, expensive and time-consuming 3D therapy. Our results of LSS+RT in adults with limb HG STS are satisfactory.

Adolescent↗
PubMed2005

A single-team experience of limb sparing approach in adults with high-grade malignant fibrous histiocytoma.

Malignant fibrous histiocytoma (MFH) is the most common subtype of soft-tissue sarcoma (STS). When located in a limb, MFH, is currently treated with limb sparing surgery (LSS) followed by radiation therapy (RT). During 8 years, 42 adult patients with high-grade limb MFH were approached by LSS and RT. Our results reflect a single-team experience and point to several important conclusions. High grade MFH, treated by conservative approach, lead to a 10-year relapse-free survival of 62% and a 10-year overall survival rate of 80%. Recurrences of MFH tend to occur during the first 2 years. Relapse-free survival was affected mainly by location in the lower limb vs. the upper limb, irrespective of the tumor size. Patients who had their diagnostic biopsies in another medical center had a greater tendency to local and systemic relapse. It seems that the most important clues for disease-free survival are the team experience and cooperation. All other factors are tumor-biology dependent, and thus far are beyond our control.

Adult↗
PubMed2004

Phosphodiesterase inhibitors as anti-cancer drugs.

It is well known that high intracellular levels of cAMP can effectively kill cancer cells in vitro. Unfortunately substances elevating cAMP such as forskolin, 8-bromo-cAMP, 8-chloro-cAMP, monobutiryl or dibutiryl cAMP are not recommended to be used as anti-cancer drugs because of their high cytotoxicity. In contrast blockers of phosphodieterases such as theophylline and aminophylline, which could elevate intracellular cAMP, are commonly used as anti-asthma drugs reaching concentrations in the blood of 10-20 microg/ml. We tested the effectiveness of theophylline and aminophylline to induce cell death alone or in combination with common anti-cancer drugs such as cisplatin and gemcitabine (gemzar). We examined such drug combinations in the induction of cell death in a variety of carcinoma cell lines derived from human ovarian, prostate and lung cancer and in granulosa cell line transformed by SV40 and Ras oncogene. While theophylline could induce moderate cell death alone, at 20-25 microg/ml concentrations, aminophylline was ineffective at this concentration. Theophylline (at 15-25 ng/ml) was found in all four representative cell lines to synergize with gemcitabine or cisplatin to induce programmed cell death, which permits a reduction in the effective doses of cisplatin and gemcitabine by 2-3-fold. The effect of theophylline in induction of apoptosis involved reduction of intracellular levels of Bcl2. Such a reduction was proportional to the extent of apoptosis induced by theophylline as well as by the combined drug treatments. Therefore, we propose that theophylline should be considered as a potential anti-cancer drug in combination with other chemotherapeutic drugs. Screening of other phosphodiesterase blockers, which are not severely toxic, could open a possibility to improved chemotherapeutic cancer treatments with reduced undesired side-effects. A clinical trial, using theophylline as an anti-cancer drug, is currently being conducted in lung cancer patients.

Animals↗
PubMed2004

Radiotherapy for spinal cord compression in patients with soft-tissue sarcoma.

PURPOSE: Spinal metastases of soft-tissue sarcoma (STS) occur rarely and pose a therapeutic problem. Although wide resection is warranted for best local control, it is rarely feasible. A radiotherapy (RT) dose of 70 Gy is usually needed to treat limb STS, but only 45 Gy can be given to the spine. In the present series, we report our experience using RT to treat spinal cord compression (SpCC) associated with STS. METHODS AND MATERIALS: The medical files of 19 adult patients with STS and SpCC were reviewed. RT was considered in all the cases, together with steroids and analgesics. The prescribed dose was 30 Gy in 10 fractions within 12 days. The effect of treatment was evaluated on a clinical basis. RESULTS: Twenty-three events of SpCC were found. The prevailing symptom was pain. The Karnofsky performance status was 40-70% at presentation. RT was given in all but 1 patient and surgical decompression in 3. Small, but important, improvements in signs and Karnofsky performance status were noted in 14 of 23 cases of SpCC, expressed mainly by pain alleviation and restoration of independence. The median survival after the diagnosis of SpCC was 5 months. CONCLUSION: Radiotherapy is an important tool in palliating SpCC in patients with STS.

Adult↗
PubMed2004

Cutaneous and subcutaneous metastases of rectal cancer.

The occurrence of cutaneous metastatic disease from colorectal cancer is uncommon and typically signifies widespread disease with poor prognosis. Colorectal metastases usually occur within the first 3 years of follow up, and the median survival of patients after the appearance of cutaneous metastatic lesions is 18 to 20 months. We describe an unusual case of a 60-year-old woman with a metachronous skin lesion as the sole site of metastatic disease, and a relatively long interval between the appearance of skin metastases and death. The woman was found to have an adenocarcinoma of the rectum, a Dukes' C lesion, extending over the entire rectal wall into the perirectal fat; five of eight regional lymph nodes showed metastases. Adjuvant radiotherapy followed by chemotherapy was administered for about 1 year. A subcutaneous lump on the left abdominal wall found 16 months postoperatively was metastatic of rectal origin. A metastatic adenocarcinoma of rectal origin was found in a single left lower axillary node 26 months later. Despite metastatic work-up for the next 2 years, an enlarged and palpated metastatic left inguinal lymph node appeared and was subjected to radiation. Computerized tomography (CT) examination 5 years after the first presentation of the rectal tumor and almost 4 years after the diagnosis of abdominal skin metastases disclosed recurrent pelvic disease with severe left hydronephrosis. Treatment by systemic chemotherapy was partially successful, but she died 8 months after this chemotherapy was initiated.

Abdominal Wall↗
PubMed2004

Successful transfer of frozen-thawed embryos obtained after subtotal colectomy for colorectal cancer and before fluorouracil-based chemotherapy.

Background. Fertility preservation is applied to patients with cancer who may be rendered sterile from chemotherapy or radiotherapy. Fluorouracil is considered as having almost no effect on human reproductive function, although clinical data defining infertility risk is negligible. Case. Controlled ovarian stimulation, in vitro fertilization (IVF), and embryo freezing were performed before fluorouracil-based chemotherapy in a 28-year-old woman who underwent subtotal colectomy for colorectal cancer (CRC). Three years later, when the clinical and hormonal analysis confirmed ovarian failure, two thawed embryos were transferred to the uterus. She gave birth at term to a 3200g infant. Discussion. Women with good prognosis who wish to bear children in the future should be offered fertility preservation options before chemotherapy, even if the likelihood of permanent ovarian failure appears to be negligible.

Adult↗
PubMed2004

Targeting metastatic leiomyosarcoma by rapamycin plus gemcitabine: an intriguing clinical observation.

The emerging anti-cancer approach is based on combining a 'traditional' cytotoxic drug with a 'signaling' blocking agent. Such combination, if designed and applied properly, may increase selectivity towards tumor cells. The use of such combinations requires smart planning and choice of the drugs to be combined, their proper dosing as well as correct sequence and schedule of application. The combination of the anti-metabolite gemcitabine and the mTOR blocker, rapamycin, has achieved an impressive response in a patient with metastatic leiomyosarcoma.

Antimetabolites, Antineoplastic↗
PubMed2003

Role of adjuvant cryosurgery in intralesional treatment of sacral tumors.

BACKGROUND: Cryosurgery is an adjuvant surgical technique for the treatment of benign aggressive, low-grade malignant and metastatic tumors of long bones. It has been used rarely to treat sacral tumors, mainly because of potential damage to nerves, blood vessels, and intrapelvic organs. The authors described their experience with this procedure and provided medium and long-term follow-up results. METHODS: Fifteen procedures of cryosurgery of the sacrum were performed in 14 patients to improve the therapeutic outcome of a variety of tumors. The patient group included 7 males and 7 females with a mean age of 42 +/- 24 years. Three patients were younger than 20 years of age. The procedures were performed at the Tel Aviv Sourasky Medical Center between January 1991 and January 1999. There were seven benign aggressive lesions (four giant cell tumors and three aneurysmal bone cysts), one benign schwannoma, one low-grade chondrosarcoma, five metastatic carcinomas, and one high-grade Ewing sarcoma, all localized at level S(2) or higher. Eight of the bone tumors also involved significant anterior or posterior soft tissue. All patients had severe preoperative pain radiating to the buttocks, perineum, and lower limbs and 9 (64%) patients had bladder and/or rectal dysfunction. Invasive diagnostic procedures and radiation (if warranted) preceded surgery. Sacral posterior fenestration and burr drilling were followed by two-cycle cryosurgery using the open pour technique or the argon-helium-based heat-freeze system. RESULTS: All interventions were performed under combined general and regional anesthesia and concluded uneventfully with moderate blood loss. Thirteen patients were discharged home after 8 +/- 5 days (one patient remained hospitalized for 30 days). Only two patients experienced local disease recurrence during a 3-11-year follow-up period: one was retreated successfully by cryosurgery and the other underwent sacrectomy and radiotherapy elsewhere, with a subsequent loss of visceral functions. No patient suffered chronic pain, deep wound infections, or significant neurologic deficits and all were satisfied with the esthetic outcome. CONCLUSIONS: Cryosurgery is a conservative, feasible, and safe adjuvant technique in the treatment of sacral tumors. It is associated with minimal permanent neurologic and vascular injury compared with sacrectomy.

Adolescent↗
PubMed2003

Comparison between two iodine-125 brachytherapy implant techniques: pre-planning and intra-operative by various dosimetry quality indicators.

PURPOSE: To prospectively compare two widely used seed implant techniques: pre-planning and intra-operative planning, based on 1 month post-implant CT-based evaluation. METHODS: We report results of a detailed 1 month post-operative dosimetric evaluation and comparison between 142 consecutive men with prostate adenocarcinoma treated by the pre-planning methodology and 214 men treated with the real-time, intra-operative seed implant method. RESULTS: Baseline parameters patient's age, Gleason score, clinical stage, and gland volume were similar in both groups (p>0.05). Length of physicist time and operating room team time were more than double in the pre-planned group compared to the intra-operative one (205 vs 100 min). Based on day 30 post-implant CT, for patients treated with the pre-planning method, mean V90, V100 and V150 (percent prostate volume receiving 90, 100 and 150% of the prescribed dose) were 67.5, 58.35 and 21.5%, respectively, while for the intra-operative group they were 97.9, 95.2 and 45%, respectively (p<0.01). Mean D90, expressed as percent of target matched peripheral dose (minimal dose covering 90% of the gland volume) was 53% for the pre-planned group and 114% for the intra-operative group of men (p<0.01). Short-term morbidity was minimal in both groups and did not correlate with the technique employed. CONCLUSIONS: This large-scale comparison of implant adequacy favours real-time intra-operative method. While all dosimetric parameters are significantly better with this method, no increased early morbidity was noted. Longer-term PSA-based clinical outcome should substantiate our contention of the superiority of the intra-operative method when compared to the pre-planning one.

Adenocarcinoma↗
PubMed2003

Computed tomography-guided core needle biopsy for bone and soft tissue tumors.

BACKGROUND: Imaging-guided core needle biopsy is a well-established technique for the diagnosis of bone and soft tissue tumors and tumor-like lesions in specialized orthopedic oncology centers. OBJECTIVE: To present our results of computed tomography-guided core needle biopsy with assessment of the accuracy of the technique. METHODS: Between July 1998 and October 2000, 215 CT-guided core needle biopsies were performed and histologically examined in the Unit of Bone and Soft Tissue Pathology, Tel Aviv Sourasky Medical Center. There were 80 soft tissue and 135 bony lesions. All biopsies were performed by the same radiologist and the histologic examination by the same pathologist. To assess the accuracy of the procedure, we compared the diagnosis at biopsy with the diagnosis after definitive surgery (when available). RESULTS: Bone core needle biopsy (n = 135) showed malignancy in 89 cases (primary or recurrent bone sarcoma, lymphoma, myeloma, metastatic carcinoma or melanoma). There were 29 benign lesions. In 17 cases the result was inconclusive and an open incisional biopsy was performed. Of the 80 soft tissue biopsies, 35 were malignant (25 soft tissue sarcomas, 6 lymphomas, 4 metastatic carcinomas); 40 were benign (myositis ossificans, neurofibroma, desmoid tumor, schwannoma, hematoma and others), and 5 were inconclusive and followed by an open incisional biopsy. The core needle biopsy histologic diagnosis was compared with that of the definitive surgery and the diagnostic accuracy was 90%. Only three samples initially diagnosed as benign turned out to be malignant. No significant complications occurred during the procedures. CONCLUSIONS: CT-guided CNB of musculoskeletal lesions is a safe and effective procedure that assures sufficient and proper material for histologic examination. The accuracy of this method in our center was 90%. Tumor sampling is extremely important, especially in soft tissue sarcomas, and cores should be taken in different directions, including areas of necrosis. The processing is quick, especially for bone CNB, and diagnosis can be achieved within 24 hours. The material undergoes excellent fixation and the immunostains are reliable.

Biopsy, Needle↗
PubMed2003

Gestation-related malignant musculoskeletal tumors.

BACKGROUND: The incidence of malignant musculoskeletal tumors during pregnancy is very low. The paucity of data precludes the drawing of solid conclusions regarding a standard approach. OBJECTIVES: To summarize our experience treating 13 pregnant women with malignant soft tissue or bone tumors. METHODS: We conducted a retrospective analysis of 13 cases of patients with either soft tissue or bone sarcoma that developed or progressed during pregnancy or immediately after delivery. RESULTS: The clinical presentation of the tumors was a growing mass and/or increasing pain and disability. Most of the masses were located in the lower part of the body and were of considerable size. Treatment given during gestation was limited to wide excision of the mass in the 28th week of gestation in one patient. All the patients reported disease progression during gestation. Vaginal delivery was possible in eight patients with no complications, cesarean section was carried out in three women, spontaneous miscarriage occurred in one and termination of pregnancy was performed in one patient. CONCLUSIONS: The diagnostic and therapeutic approaches should be tailored specifically in every pregnant woman in whom sarcoma is suspected.

Adult↗
PubMed2002

Lack of ErbB-2 oncogene product overexpression in soft tissue sarcomas.

The c-erbB-2 gene and its products (also designated HER-2 and c-neu) encode for a 185-kd transmembrane glycoprotein with intracellular tyrosine kinase activity. c-erbB-2 belongs to the epidermal growth factor receptor family, of which there are four known members, and has molecular homology to the epidermal growth factor receptor. It seems that this family is critical in control of growth, differentiation, and mobility of many normal and transformed epithelial cell types. We have looked for overexpression of c-erbB-2 gene product in paraffin-embedded material from 230 cases of soft tissue sarcoma, in order to establish a possible new prognostic marker and a potentially new treatment option. In all the cases, irrespective of the sarcoma histological type, the immunostaining for erbB-2 was negative. Applications of erbB-2 for prognostication as well as the option of receptor targeting by trastuzumab monoclonal antibodies were aborted.

Adolescent↗
PubMed2002

A possible role for IVIg in the treatment of soft tissue sarcoma: a clinical case and an experimental model.

A patient with a malignant peripheral nerve sheath tumor (MPNST) was treated with IVIg for multiple sclerosis. Her MPNST course was remarkably longer and more indolent than expected; she achieved a disease-free interval (DFI) of 30 months. Seven other patients, who were not treated by IVIg, had a relatively aggressive course (median DFI 3 months). These results led us to examine the effect of IVIg on the growth of sarcoma in vitro and in vivo in an experimental model of MCA-bearing mice. When added to MCA-105 sarcoma cell cultures, IVIg produced a dose-dependent inhibitory effect on [(3)H]-thymidine incorporation. The maximal inhibitory effect was at a concentration of 50 mg/ml IVIg. Cell cycle analysis revealed a hypodiploid peak at the lower fluorescence values which appeared in the samples treated with IVIg. These results demonstrate that the anti-proliferative activity results from an apoptotic effect of IVIg on the tumor cells. In a second set of experiments, we evaluated the capability of IVIg, when administered orally or subcutaneously, to inhibit the growth of MCA-105 sarcoma lung metastases. A decrease in the mean lung weight was observed in the mice that were treated by s.c. or oral administration, the latter being more effective. A possible role for IVIg in the treatment of MPNST and other soft tissue sarcomas is suggested.

Animals↗
PubMedDate not supplied

Sarcoma and thyroid disorders: a common etiology?

We have recently observed that many of our sarcoma patients presented also with thyroid disorders. Literature data are almost unavailable on this topic. The relationship between the sarcoma and thyroid disorders is examined. Retrospective analysis of files of patients with sarcoma and clinically overt thyroid disorders was carried out. Of the 375 patients with soft tissue sarcomas (STS) and 235 with bone sarcoma (BS) including small blue round cell tumors (SBRC), 28 patients (4.6%) had an associated significant thyroid disorder. The types of sarcoma were mainly liposarcoma followed by malignant fibrous histiocytoma, leiomyosarcoma and bone sarcoma. The primary sites were mainly limb and trunk. The interval between the diagnosis of the thyroid disorder and the sarcoma varied between -14 years (thyroid first) and +16.5 years (thyroid later) with a median of -0.2 years. Thyroid disorders included goiter, thyroiditis and carcinoma. There are both basic-science and clinical evidence to a possible common pathway that leads to the association between overt thyroid disorders and sarcomas of bone or soft tissues. Oncogene erbA activity is related to thyroid receptors to T3 and to development of sarcoma. Cross talk of the sarcoma oncogene and the erbA might contribute to the development of sarcoma. The thyroid hormone receptor and the highly related viral oncoprotein v-erbA are found exclusively in the nucleus as stable constituents of chromatin. It has been shown that v-erbA can block the spontaneous differentiation in erythroid cells transformed by various retroviral oncogenes. V-erbA can alter the spectrum of neoplasia induced by the v-src oncogene, which causes predominantly sarcomas and erythroblastosis in chicks. The erbA can cooperate with other oncogenes such as v-erbB or with v-fms, v-ras, and c-kit. Cooperation with v-myc may play a role in the development of rhabdomyosarcoma especially in thyroid hormone deficiency state. The possible clinical implications are the need to screen patients with sarcoma to thyroid disorders, and patients with thyroid disorders for malignant diseases.

Adult↗
PubMedDate not supplied

The role of interleukin-8 in the initiation and progression of human cutaneous melanoma.

BACKGROUND: The expression of Interleukin-8 (IL-8) by human melanoma cells correlates with their metastatic potential in vitro and in nude mice. The role of IL-8 in human patients is not yet clear. The purpose of the present study was to search for a possible correlation between IL-8 in patients' melanoma specimens and the clinical course of the disease. PATIENTS AND METHODS: All patients operated on for malignant melanoma (MM) at our center between 1985 and 1993 were screened for the study. Only those with retrievable pathological and clinical material were included. IL-8 tumor levels were tested by immunohistochemistry. RESULTS: Seventy-four patients were eligible for inclusion in the study. In 49, the primary tumor was analyzed and in 25 a metastasis. IL-8 was expressed in 91% of the primary lesions, 70% of the lymph node metastasis and 70% in local recurrence or in-transit metastases. There was no correlation between level of expression and outcome. Comparing IL-8 expression in primary and secondary lesions of the same patient showed a trend towards better survival for those who had down-expression of IL-8. CONCLUSION: IL-8 is over-expressed in cutaneous MM. Although no direct correlation was found in the present study between IL-8 expression and survival, it would appear that IL-8 plays a major role in melanoma development.

Adolescent↗