Control of cell proliferation by heparan sulfate and heparin-binding growth factors.
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Animals↗
Biomedical subjects
T Peretz
Publications and source records attributed to T Peretz.
Ovarian stimulation and breast cancer: is there a link?
The results of both epidemiologic and experimental studies suggest that endogenous (and apparently exogenous) sex hormones and other reproductive variables have an important role in the development of human breast neoplasia. Nevertheless, no controlled study has ever addressed the possible effects of ovarian stimulation on the incidence and course of human breast cancer. Over the past decade the number of women undergoing follicular stimulation, especially during assisted reproductive technology procedures, has grown rapidly. Here we present 16 cases of young women who were treated by induction of ovulation, and subsequently were diagnosed with breast cancer. These women were drawn out of 950 cases of infertile women who underwent induction of ovulation at our fertility clinic over a 10-year period. The possible association between ovarian stimulation and promotion of breast cancer is discussed and the need for a controlled study is emphasized.
Adult↗
Psychological distress in female cancer patients with Holocaust experience.
This study examined whether severe emotional and physical trauma in the past affects the psychological condition of female patients currently afflicted with cancer. Using the Brief Symptom Inventory (BSI), 41 women with cancer, who had sustained extreme trauma during the Nazi Holocaust of the midcentury, were compared with three different groups: a matched group of cancer patients without Holocaust experience, a physically healthy group of female Holocaust survivors, and healthy women without a Holocaust past. Although psychological distress was comparable in the two healthy groups, it was far higher in Holocaust cancer patients than in either their non-Holocaust counterparts or in the group of healthy Holocaust survivors. These results may suggest that the severe trauma of the Holocaust could be responsible for markedly diminished psychological response when such patients are confronted with new stress.
Aged↗
Clinical studies of liposome-encapsulated doxorubicin.
Initial clinical studies with doxorubicin entrapped in the bilayer of phosphatidylglycerol-rich liposomes were hindered by the avid reticuloendothelial system (RES) uptake and by drug leakage from circulating liposomes. In contrast, recent tests of a doxorubicin formulation of polyethyleneglycol-coated liposomes (Doxil) in cancer patients indicate that the drug pharmacokinetic properties are significantly altered, with a prolonged distribution half-life of approximately 2 days. Plasma fractionation studies show that nearly all the drug measured in plasma is in liposome-encapsulated form. The dose of Doxil has been escalated from 25 to 60 mg/m2. Stomatitis is the most significant toxicity, and skin toxicity, in the form of hand-foot syndrome, may complicate the repeated administration of Doxil. A number of objective antitumor responses in a variety of malignancies have been observed, indicating that Doxil is an active antitumor compound. Polyethyleneglycol-coated liposomes show a distinct advantage over previous liposome formulations directed at the RES and appear to be a promising drug delivery system for doxorubicin.
Adult↗
Taxol: initial Israeli experience with a novel anticancer agent.
Taxol is a novel taxane derivative obtained from the bark of the Pacific yew, Taxus brevifolia, which has demonstrated substantial antitumor activity in early clinical trials. Intensive research efforts were necessary to overcome both supply problems and hypersensitivity reactions to the drug and thus assure its widespread use. Taxol is active in a variety of neoplasias, including advanced breast and ovarian tumors resistant to drugs such as doxorubicin and cisplatin, respectively. We report here the initial experience with taxol in these two disease entities in Israel, at three institutions within the framework of large multinational trials. These studies compared a) the use of two dose levels of taxol, and b) short, 3-h administration vs. a longer 24-h infusion of the drug. A total of 107 Israeli patients, 38 with ovarian cancer and 69 with breast cancer, were given 706 courses of taxol. Our results show that the administration of taxol at doses ranging between 135 and 175 mg/m2 is indeed feasible and that 3-h infusions are as well tolerated as longer administration. The main hematological toxicity was leukopenia, which was promptly reversible and was more pronounced both at the higher dose level and with the more prolonged infusion. Of the nonhematological side effects, the most prominent were alopecia, mild nausea and vomiting, limb paresthesias, fatigue and myalgia. Allergic reactions following routine premedication were mild and infrequent, never necessitating discontinuation of the drug. Clinically significant cardiac events did not occur. Taxol is an important addition to the anticancer chemotherapy armamentarium.
Adult↗
Holocaust cancer patients: a comparative study.
There is as yet no consensus on the long-term effects of severe life-threatening stresses. In an earlier study (Baider et al. 1992), we gained some understanding of this issue by addressing a specific question: How do individuals who have undergone severe stress in the past cope with a current stress? We investigated whether severe stress occurring in the past had a long-term effect on present coping capabilities. We addressed the question by studying a group of Holocaust survivors (severe past stress) who were diagnosed as having cancer (current stress) and compared them to a matched group of cancer patients with no past history of trauma. The matching was done on most demographic variables (gender, age, marital status, and education), as well as on disease variables (site and stage of cancer, time since cancer diagnosis, previous and present treatments). The results were unequivocal.
Adaptation, Psychological↗
Effect of the Holocaust on coping with cancer.
The aim of the study was to investigate whether surviving stressful life threatening situations influences coping with new stressful life threatening situations. The study group, therefore, was composed of 53 cancer patients (present life threatening situation) who had survived the Holocaust (past life threatening situation). They were compared to 53 cancer patients who had not gone through the Holocaust, matched for sociodemographic and medical background. The Holocaust survivors were unable to mobilize partial denial (had significantly higher scores on the Impact of Events Scale) and their psychological distress was much higher (significantly higher scores on the Brief Symptom Inventory). Their functioning however (as reported along the Psychosocial Adjustment to Physical Illness Scale) did not significantly differ from that of the comparison group. The possible mechanisms for these long term effects of past trauma are discussed as well as the need to regard traumatized persons as 'high risk' psychologically when they have to cope with new life threatening situations.
Adaptation, Psychological↗
Pharmacokinetic and imaging studies in patients receiving a formulation of liposome-associated adriamycin.
Pharmacokinetic and imaging studies in 19 patients receiving liposome-entrapped adriamycin (L-ADM) were carried out within the framework of a Phase I clinical trial (Gabizon et al., 1989a). The formulation of L-ADM tested consisted of 0.2 microM-extruded multilamellar vesicles composed of egg phosphatidylcholine, egg-derived phosphatidyl-glycerol (PG), cholesterol, and ADM intercalated in the fluid lipid bilayer. Plasma clearance of total drug extracted from the plasma after L-ADM infusion followed a biexponential curve with a pattern similar to that reported for free ADM. The plasma concentration of drug circulating in liposome-associated from was also measured in a subgroup of seven patients. Liposome-associated drug was found to be rapidly cleared from plasma. Its ratio to non-liposome-associated drug appeared to correlate with liver reserve, with highest ratios in patients with normal liver function. Liposome clearance, as measured by the plasma concentration of PG in three patients was slower than the clearance of liposome-associated ADM, suggesting that liposomes lose part of their drug payload during circulation. To learn about the liposome organ distribution, imaging studies were carried out with 111Indium-deferoxamine labelled liposomes of the same composition. Liposomes were cleared predominantly by liver and spleen and to a lesser extent by bone marrow in seven out of nine patients. In two patients with active hepatitis and severe liver dysfunction, there was minimal liver uptake and increased spleen and bone marrow uptake. Except for one hepatoma patient, intrahepatic and extrahepatic tumours were not imaged by liposomes, suggesting that liposome uptake is restricted to cells of the reticulo-endothelial system (RES).(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Maintenance on extracellular matrix and expression of heparanase activity by human ovarian carcinoma cells from biopsy specimens.
A routine procedure has been developed for the isolation and maintenance in culture of human ovarian carcinoma cells derived from biopsy specimens. Cell attachment, plating efficiency and initial outgrowth were greatly improved by seeding the cells on a basement-membrane-like extracellular matrix (ECM) deposited by cultured corneal endothelial cells. These effects were most significant in serum-free conditions which markedly reduced the rate of cell attachment and growth on regular tissue culture plastic. In 60-80% of the cases and regardless of the patient's age, cells cultured on ECM in the absence of serum divided actively and formed a tightly packed epithelial cell monolayer. Fibroblast overgrowth and cell detachment often occurred on ECM in the presence of serum. Incubation of the human ovarian carcinoma cells with sulfate-labelled ECM, resulted in the release of heparan sulfate degradation fragments, 4- to 7-fold smaller than intact heparan sulfate side chains. This degradation was brought about by endoglycosidase (heparanase) activity expressed to a higher extent by cells that were first maintained in primary cultures as compared with cell aggregates taken directly from the biopsy specimen. In most cases, cells derived from metastatic tumors expressed a higher heparanase activity than cells from the primary ovarian tumor. This result corroborates previous studies, performed with cell lines, on the possible involvement of heparanase in tumor cell invasion and metastasis.
Autoradiography↗
Primary colorectal sarcoma. A retrospective review and prognostic factor study of 50 consecutive patients.
Fifty patients were admitted to Memorial Hospital, Memorial Sloan-Kettering Cancer Center, New York, NY, with primary colorectal sarcoma between 1948 and 1987. Thirty-one patients (62%) presented with a high-grade tumor, 37 patients (74%) with a tumor larger than 5 cm, and 12 patients (24%) with metastasis. The median survival of the whole group was 33 months, and the median survival of patients who underwent curative operation was 174 months. Nineteen of 32 patients who underwent curative operation were observed to develop distant metastasis after 3 to 209 months. The dominant sites of metastatic disease were the liver and peritoneal cavity. In a multivariable analysis, noncurative treatment and high-grade tumor were the only prognostic factors unfavorably affecting tumor-related mortality. If the type of treatment received was not considered, presentation with metastatic disease and a high-grade tumor were the two unfavorable characteristics that had independent prognostic value. Patients with a tumor that was larger than 5 cm or that was located in the colon had a greater likelihood of having a palliative procedure or high-grade tumor.
Adolescent↗
Radiocurability of microscopic disease in childhood rhabdomyosarcoma with radiation doses less than 4,000 cGy.
In an attempt to evaluate the radiocurability of microscopic disease in childhood rhabdomyosarcoma (RMS) with total tumor doses of less than 4,000 cGy, we performed a retrospective analysis of all patients with microscopic residual RMS who were treated at the Memorial Sloan-Kettering Cancer Center (MSKCC) during the years 1970 to 1987. There were 32 patients ranging in age from 3 months to 22 years (median, 6 years) with microscopic residual of either (1) a localized primary tumor (MSKCC, stage IB; Intergroup Rhabdomyosarcoma Study [IRS] group IIA), 19 patients; or (2) an involved lymph node region with the primary tumor completely resected (MSKCC stage III; IRS group IIC), 13 patients. Twenty-nine of the 32 patients presented with embryonal histology. All patients were treated with combination chemotherapy (CT) and megavoltage external beam radiotherapy (RT). The RT was delivered in either conventional fractionation of 180 to 200 cGy daily (30 patients) or hyperfractionation of 150 cGy twice daily (two patients). Fifteen patients received RT doses of less than 4,000 cGy with a range of 3,000 to 3,600 cGy and a median value of 3,100 cGy; 17 patients received 4,000 cGy or more with a range of 4,000 to 6,000 cGy and a median value of 4,600 cGy. With a median follow-up of 11 years, the relapse-free survival was 25 of 32 patients (less than 4,000 cGy, 12 of 15; greater than or equal to 4,000 cGy, 13 of 17). The RT local control rate was 30 of 32 (less than 4,000 cGy, 14 of 15; greater than or equal to 4,000 cGy, 16 of 17 [P = .94]). Our results suggest that radiation doses of below 4,000 cGy, when combined with effective multiagent CT, may be sufficient for local control of microscopic disease in childhood embryonal RMS.
Adolescent↗
New intraoperative brachytherapy techniques for positive or close surgical margins.
Tumors attached or adjacent to critical structures can often not be completely resected or resected with adequate surgical margins. Sites involving major blood vessels, the paravertebral spaces, or critical abdominal structures often present technical difficulties for standard brachytherapy procedures using I-125 or Ir-192 implants. These techniques allow for a high-dose delivery to the tumor bed with minimal normal tissue toxicity. A relatively simple and accurate method is described using I-125 seeds in Vicryl suture threaded through Gelfoam. These permanent implant procedures with radioactive I-125 seeds effectively treat small residual tumors or suspicious margins where standard brachytherapy techniques may be unsatisfactory and technically difficult to perform.
Adult↗
Cisplatin, bleomycin, and methotrexate (PBM) chemotherapy in locally advanced and metastatic head and neck cancer.
Twenty-two patients with locally advanced or metastatic head and neck tumors received a total of 84 courses of a combination of cisplatin, bleomycin, and Methotrexate (PBM) for a median of four courses per patient (range, 1-7). Among these 22 patients there were four patients (18%) who achieved complete remission (CR) and 13 patients (60%) who had a partial remission (PR). The overall remission rate (CR + PR) thus reached 78%; five patients (22%) progressed while on therapy. The mean duration of objective response (CR + PR) was 8 months; CR lasted a median of 18 months (range, 2-48). Survival was not influenced by tumor histology or by previous surgery. The presence of locoregional disease did adversely affect survival from the onset of chemotherapy (P = 0.1). The rate of survival was also affected by primary tumor site; patients with nasopharyngeal primaries survived longer than all other patients (22 vs. 11 months, P = 0.06). Toxicity to chemotherapy consisted mainly of nausea and vomiting and stomatitis. Three patients developed fever while leukopenic. One patient experienced irreversible renal damage, and another suffered from bleomycin-induced pulmonary fibrosis. The high response rate obtained in our group of patients did not have a substantial impact on overall survival. Aggressive, multimodality approaches should be considered in the treatment of these patients when possible.
Antineoplastic Combined Chemotherapy Protocols↗
Systemic administration of doxorubicin-containing liposomes in cancer patients: a phase I study.
A clinical study was designed to evaluate the tolerance of cancer patients to liposome-associated doxorubicin (L-DXR). The liposomes used contain phosphatidylglycerol, phosphatidylcholine, cholesterol, and DXR intercalated in the lipid bilayer, and have a mean size in the range of 0.3-0.5 microns. Thirty-two patients, most of them with primary or metastatic liver cancer refractory to conventional therapy, were entered into the study. A total of 69 courses of therapy was administered by intravenous infusion of a suspension of L-DXR (0.5-2.0 mg DXR/ml) in physiologic saline at an approximate rate of 2 ml/min given on a 3-week intermittent schedule. The L-DXR and phospholipid doses were escalated from 20 mg/m2 and 0.3 g/m2 to 120 mg/m2 and 3.2 g/m2 respectively. Treatment was generally well tolerated and acute toxic effects such as nausea and vomiting were mild and infrequent. Chills and fever (greater than 38.0 degrees C) were observed in three patients during infusion of L-DXR and in seven patients 6-12 h after the end of infusion. Median WBC nadir counts were 2700, 2300 and 700/microliters at 85, 100 and 120 mg/m2 respectively. All three patients receiving 120 mg/m2 developed grade 4 leukopenia and fever requiring intravenous antibiotics, and, in two of them, severe stomatitis (grades 3 and 4) was observed. Significant hair loss was apparent in all patients receiving doses higher than 50 mg/m2. The maximal tolerated dose of L-DXR appears to be 120 mg/m2, with leukopenia and stomatitis being the dose-limiting factors. While the subacute toxicity of L-DXR appears to be qualitatively similar to that of free DXR, its tolerance exceeds the recommended dose of free DXR (75 mg/m2) in the standard 3-weekly schedule.
Adult↗
Treatment of primary unresectable carcinoma of the pancreas with I-125 implantation.
Between January 1 1974 and October 31 1987, 98 patients with biopsy proven unresectable adenocarcinoma of the pancreas were treated with I-125 implants during laparotomy. Presenting symptoms were pain (57 patients), jaundice (45 patients), and weight loss (34 patients). All patients underwent laparotomy and surgical staging. Thirty patients had T1NoMo disease, 47 patients had T2-3NoMo disease, and 21 patients had significant regional lymph node involvement (T1-3N1Mo). The surgical procedure performed was biopsy only (16 patients), gastric bypass (36 patients), biliary bypass (49 patients), and partial or total pancreatectomy with incomplete resection (5 patients). The total activity and the number of seeds used were determined from the Memorial Sloan Kettering Cancer Center (MSKCC) nomogram. Stereoshift localization X ray films were taken 3-6 days after operation. The mean activity, minimal peripheral dose (MPD), and volume of the implants were 35 mCi, 13,660 cGy, and 53 cm3, respectively. In addition, 27 patients received postoperative external irradiation and 27 patients received chemotherapy. Postoperative complications were observed in 19 patients. These included post-operative death (1 patient), biliary fistula (4), intraabdominal abscess (4), GI bleeding (3), gastric or small bowel obstruction (6), sepsis (5), and deep vein thrombophlebitis (4). Pain relief was obtained in 37/57 patients (65%) presenting with pain. A multivariate analysis showed that four factors significantly affected survival: T stage, N stage, administration of chemotherapy, and more than 30% reduction in the size of the implant on follow-up films. The median survival for the entire group was 7 months. A subgroup of patients with T1No stage disease who received chemotherapy survived 18.5 months. The indications for I-125 seed implantation in unresectable carcinoma of the pancreas are discussed.
Adenocarcinoma↗
Duodenal epithelial atypia. A specific complication of hepatic arterial infusion chemotherapy.
Severe duodenal lesions developed in five patients during hepatic arterial infusion (HAI) employing 5-floxuridine (FUDR) as the basic antineoplastic agent. These lesions comprised ulcerative as well as proliferative processes. Striking structural distortion with cellular pleomorphism of the affected duodenal mucosa were the histological hallmark in all cases. These lesions are a specific complication of HAI chemotherapy and should not be misinterpreted as malignancy.
Adult↗
Combined 5-fluorouracil and radiation therapy following resection of locally advanced gastric carcinoma: a 5-years follow-up.
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Adult↗
Giant duodenal ulcer: the hepatic intra-arterial chemotherapy variant.
Giant duodenal ulcers are extensive ulcers, more than 2.5 cm in diameter, that involve a large portion of the duodenal bulb. These atypical duodenal ulcers create serious problems to the patient and the physician, are frequently complicated by bleeding and penetration, and have a high mortality rate. Most of the reported cases were classified as a severe variant of the common peptic ulcer disease, others were associated with the Zollinger Ellison syndrome. We report here four patients with giant duodenal ulcers but with a different and definitive aetiology: hepatic intra-arterial chemotherapy infusion for liver metastase or primary hepatocellular carcinoma.
Adult↗