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Biomedical subjects

R Catane

Publications and source records attributed to R Catane.

At least 37 records · Page 2Linked to original sources
PubMed1996

The protective role of the immunomodulator AS101 against chemotherapy-induced alopecia studies on human and animal models.

The immunomodulator AS101 has been demonstrated to exhibit radioprotective and chemoprotective effects in mice. Following phase-I studies, preliminary results from phase-II clinical trials on non-small-cell-lung-cancer patients showed a reduction in the severity of alopecia in patients treated with AS101 in combination with chemotherapy. To further substantiate these findings, the present study was extended to include 58 patients treated either with the optimal dose of 3 mg/m2 AS101 combined with carboplatin and VP-16, or with chemotherapy alone. As compared with patients treated with chemotherapy alone, there was a significant decrease in the level of alopecia in patients receiving the combined therapy. The newly developed rat model was used to elucidate the protective mechanism involved in this effect. We show that significant prevention of chemotherapy-induced alopecia is obtained in rats treated with Ara-C combined with AS101, administered i.p. or s.c. or applied topically to the dorsal skin. We show that this protection by AS101 is mediated by macrophage-derived factors induced by AS101. Protection by AS101 can be ascribed, at least in part, to IL-1, since treatment of rats with IL-1 RA largely abrogated the protective effect of AS101. Moreover, we demonstrate that in humans there is an inverse correlation between the grade of alopecia and the increase in IL-1 alpha. In addition, protection by AS101 could be related to PGE2 secretion, since injection of indomethacin before treatment with AS101 and Ara-C partly abrogated the protective effect of AS101. To assess the ability of AS101 to protect against chemotherapy-induced alopecia, phase-II clinical trials have been initiated with cancer patients suffering from various malignancies.

Alopecia↗
PubMed1996

Palliative medicine and the medical oncologist. Defining the purview of care.

The fusion of palliative medicine and medical oncology, in practice and in education, can provide a better standard of patient care, reduce the risk of oncologist burnout, and increase the likelihood of patient family and physician satisfaction. There need be no gulf between these disciplines, and only together do they represent truly comprehensive cancer care. The realization of this fusion will require the participation of individual clinicians, program directors, and the policy makers for cancer centers, professional organizations, and the health care regulatory authorities. It is a logical next step in the evolution of medical oncology.

Hospice Care↗
PubMed1995

Bone marrow-sparing and prevention of alopecia by AS101 in non-small-cell lung cancer patients treated with carboplatin and etoposide.

PURPOSE: The aim of this study was to evaluate the ability of the immunomodulator AS101 to prevent chemotherapy-induced neutropenia and thrombocytopenia and thus allow patients to receive full-dose antineoplastic agents according to protocol design. We also aimed to determine the production level of various hematopoietic growth factors in treated patients. PATIENTS AND METHODS: This study of 44 unresectable or metastatic non-small-cell lung cancer (NSCLC) patients was an open-label prospective randomized study of standard chemotherapy alone versus chemotherapy plus AS101. Each patient received carboplatin (300 mg/m2 intravenously [IV] on day 1 of a 28-day cycle, and etoposide (VP-16) (200 mg/m2 orally) on days 3, 5, and 7 of each cycle. AS101 was administered at 3 mg/m2 three times per week starting 2 weeks before chemotherapy. RESULTS: AS101, which manifested no major toxicity, significantly reduced neutropenia and thrombocytopenia and thus allowed all treated patients to receive full-dose antineoplastic agents, in contrast to only 28.5% of the control group. Continuous treatment with AS101 significantly reduced the number of days per patient of thrombocytopenia and neutropenia and did not provide protection to tumor cells as reflected by the higher overall response rate compared with the chemotherapy-alone arm. Interestingly, AS101 treatment also significantly prevented chemotherapy-induced alopecia. These effects correlate with the ability of AS101-treated patients to increase significantly the production of colony-stimulating factors (CSFs) interleukin-1 alpha (IL-1 alpha) and IL-6. CONCLUSION: AS101 has significant bone marrow (BM)-sparing effects and prevents hair loss in chemotherapy-treated patients, with minimal overall toxicity. These effects are probably due to increased production of IL-1 alpha, IL-6, and granulocyte-macrophage (GM)-CSF.

Adjuvants, Immunologic↗
PubMed1994

Prolonged circulation time and enhanced accumulation in malignant exudates of doxorubicin encapsulated in polyethylene-glycol coated liposomes.

In preclinical studies, a doxorubicin liposome formulation containing polyethylene-glycol (Doxil) shows a long circulation time in plasma, enhanced accumulation in murine tumors, and a superior therapeutic activity over free (unencapsulated) doxorubicin (DOX). The purpose of this study was to characterize the pharmacokinetics of Doxil in cancer patients in comparison with free DOX and examine its accumulation in malignant effusions. The pharmacokinetics of doxorubicin and/or liposome-associated doxorubicin were analyzed in seven patients after injections of equivalent doses of free DOX and Doxil and in an additional group of nine patients after injection of Doxil only. Two dose levels were examined, 25 and 50 mg/m2. When possible, drug levels were also measured in malignant effusions. The plasma elimination of Doxil followed a biexponential curve with half-lives of 2 and 45 h (median values), most of the dose being cleared from plasma under the longer half-life. Nearly 100% of the drug detected in plasma after Doxil injection was in liposome-encapsulated form. A slow plasma clearance (0.1 liter/h for Doxil versus 45 liters/h for free DOX) and a small volume of distribution (4 liters for Doxil versus 254 liters for free DOX) are characteristic of Doxil. Doxorubicin metabolites were detected in the urine of Doxil-treated patients with a pattern similar to that reported for free DOX, although the overall urinary excretion of drug and metabolites was significantly reduced. Doxil treatment resulted in a 4- to 16-fold enhancement of drug levels in malignant effusions, peaking between 3 to 7 days after injection. Stomatitis related to Doxil occurred in 5 of 15 evaluable patients and appears to be the most significant side effect in heavily pretreated patients. The results of this study are consistent with preclinical findings indicating that the pharmacokinetics of doxorubicin are drastically altered using Doxil and follow a pattern dictated by the liposome carrier. The enhanced drug accumulation in malignant effusions is apparently related to liposome longevity in circulation. Further clinical investigation is needed to establish the relevance of these findings with regard to the ability of liposomes to modify the delivery of doxorubicin to solid tumors and its pattern of antitumor activity.

Adult↗
PubMed1994

Tumor lysis syndrome in nonhematologic malignancies. Report of a case and review of the literature.

Tumor lysis syndrome (TLS), resulting from massive necrosis of neoplastic cells after chemotherapy, is a rare complication in nonhematologic malignancies. A 32-year-old woman suffering from a rapidly progressing breast adenocarcinoma metastatic to the liver and bones received a course of single-agent chemotherapy with mitoxanthrone and 4 days later developed the tumor lysis syndrome, and subsequently acute renal failure. The patient responded well to appropriate treatment. This case report points out that breast cancer can be extremely sensitive to chemotherapy and suggests that prophylaxis for tumor lysis syndrome should be considered in the subset of patients with breast carcinoma who have hepatic metastases and large tumor burdens.

Adult↗
PubMed1994

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↗
PubMed1993

Noninvasive follow-up of platinum pharmacokinetics in the skin of patients on cisplatin chemotherapy.

BACKGROUND: Treatment with high-dose cisdiammine-dichloroplatinum (II) (cisplatin, cDDP) often is associated with late complications, predominated by peripheral neuropathy. Pt deposition in different tissues may play a key role in the induction of many of these effects. Main topics of interest include the relationship between cDDP doses given during treatment and the long-term pharmacokinetics of the drug complexes in normal tissues and blood. Noninvasive examination of Pt in tissues during and after cDDP treatment are needed to clarify these points. METHODS: A novel, high-sensitivity diagnostic x-ray spectrometry (DXS) method was used for the fast, noninvasive analysis of Pt in external tissues of patients with cancer treated with courses of cDDP. The Pt in a small skin area was excited by a monochromatic soft x-ray beam (14.6 KeV) and the spectral L lines emitted from the tissue were detected. A limit of detection below 1 microgram/g wet weight was reached. The pharmacokinetics of Pt in blood was investigated in parallel with the use of high-sensitivity, flameless atomic absorption spectrometry (AAS). RESULTS: Follow-up of Pt concentrations in the skin of patients with cancer by DXS before cDDP treatment, during treatment, and up to 4 months after its completion, showed prolonged Pt deposition that corresponded to the net cumulative doses of the drug. Pt clearance from the skin fitted a monoexponential curve with a half-life of about 30 days. In comparison, the pharmacokinetics of total Pt in plasma showed a much faster, biexponential clearance with half-lives of 41 minutes and 5.2 days, respectively. CONCLUSIONS: The amount of nonspecific Pt deposition in the tissues was found to depend on the total doses administered, the time interval between the courses, and the slow rate of clearance. Noninvasive measurements of tissue Pt levels may serve as a major tool in the evaluation of the induction of late cDDP complications.

Cisplatin↗
PubMed1993

Recurrence-associated mortality in patients with differentiated thyroid carcinoma.

Differentiated thyroid carcinoma (DTC) is associated with prolonged natural history, and even recurrent tumor is not necessarily followed by increased mortality. Prognostic factors and different treatment strategies, therefore, are difficult to assess. One hundred and fifty-seven patients were followed in our clinic. In an attempt to predict mortality from this tumor, we evaluated the risk factors in 36 patients who presented with recurrent disease. Ten of these patients died. Age above 40 years at initial diagnosis was the predominant risk factor associated with 44% mortality after recurrence. Male sex, lack of radioiodine treatment, and distant site of initial recurrence were all associated with a trend towards increased mortality. Tumor histology and local invasion or extent of initial surgical treatment failed to affect mortality. In conclusion, this approach may be used to identify those patients who will die from their disease, despite currently available treatment. It remains to be seen, however, if new treatment protocols can be developed to improve the prognosis of these patients.

Adenocarcinoma↗
PubMed1993

Estimation of creatinine clearance without 24-hour urine collection--a useful guide during cisplatin therapy.

The validity of the Cockroft and Gault formula in monitoring renal function during cisplatin therapy was examined in 110 consecutive cancer patients. A good correlation between estimated creatinine clearance (ECC) and the standard measured creatinine clearance (MCC) was found both before and after the onset of cisplatin. The correlation was better in males (r = 0.78 prior to cisplatin and r = 0.79 after the initiation of cisplatin) than in females (r = 0.69 and r = 0.63 respectively). Obesity (> 125% of ideal body weight) had no major effect on the correlation between ECC and MCC. The presence of third-space body fluids, on the other hand, had an influence on the relations between ECC and MCC, particularly in females (r = 0.49). It is concluded that estimation of creatinine clearance, without the cumbersome collection of 24-h urine specimens, is accurate enough for the purpose of adjusting cisplatin dose. It should not be used in females with third-space body fluids.

Adolescent↗
PubMed1993

Overview of Taxol safety.

The safety profile of Taxol administered intravenously as a single agent has been established based on the experience of 655 patients. Of these patients, 253 were treated in nine phase I studies, and 402 were treated in eight disease-oriented phase II studies. Myelosuppression, specifically neutropenia, was the dose-limiting toxicity in all studies conducted in patients with solid tumors. Neutropenia was schedule dependent and was less severe when Taxol was administered via a 3-hour infusion. Severe hypersensitivity reactions were controlled in the phase II program with a premedication regimen consisting of dexamethasone, an antihistamine, and an H2 blocker. Cardiovascular toxicities were minimal and do not indicate constant electrocardiographic monitoring during Taxol infusions. Peripheral neuropathy was usually mild to moderate and dose related; however, it rarely caused treatment discontinuation. Additional adverse events associated with Taxol include arthralgia/myalgia, mucositis, nausea and vomiting, and alopecia.

Bone Marrow↗
PubMed1990

Tuftsin induces tissue factor-like activity in human mononuclear cells and in monocytic cell lines.

Normal human monocytes and macrophages generate potent procoagulant activity (PCA) resembling tissue factor (TF) in response to various stimuli. In this study we show that tuftsin, a natural stimulator of many functions of monocytes and macrophages, also stimulates a potent PCA in mixed mononuclear cells and monocytes, and a mild PCA in lymphocytes and cell lines of monocytic origin (U937 and THP). No activity was generated by several lymphoid cell lines and HL-60 cells. The PCA resembled TF in that it accelerated clotting through the extrinsic coagulation pathway and was inhibited by concanavalin-A and by monoclonal anti-TF antibodies. The induction of TF-like activity by tuftsin was dose- and time-dependent. It was located in the cell membrane and did not require T cells for expression. Generation of TF-like activity was prevented by actinomycin D, while cytarabine had no effect on this process, suggesting that expression of the activity depends on protein synthesis. Studies with various tuftsin analogs suggest that tuftsin stimulates generation of TF-like activity, as well as other functions of monocytes via the same receptors. The results with the monocytic cell lines show that tuftsin affects mainly mature cells. The induction of TF-like activity in mononuclear cells by tuftsin constitutes an important link between mononuclear cells and the immune and coagulation systems. It may play a major role in the pathogenesis of thromboembolism and fibrin deposition in various inflammatory and immunologic disorders.

Blood Coagulation Factors↗
PubMed1990

Polytuftsin: a potential precursor for slow release of the phagocytosis stimulating peptide tuftsin.

1. Polytuftsin (Thr-Lys-Pro-Arg)n, was synthesized through polycondensation of an amino-free and carboxyl-activated derivative of tuftsin, H2N-Thr-Lys(Z)-Pro-Arg(Tos)-OSu, following suitable deprotection and fractionation steps. 2. Digestion of polytuftsin by trypsin, as well as by normal human serum, at 37 degrees C, yielded free tuftsin. 3. Polytuftsin affected the decreased formation of lung-metastasis, in B16 melanoma treated mice and prolonged the survival of animals more efficiently than tuftsin. 4. Tuftsin was found to be totally degraded by serum enzymes within approximately 60 min at 37 degrees C.

Amino Acid Sequence↗
PubMed1990

The use of monoclonal anti-CEA antibody immunohistochemistry in detecting the origin of oral cavity metastasis.

A 75-year-old woman presented with a painless swelling in the right mandibular retromolar area and numbness of the left lower lip. Radiographic examination of the mandible demonstrated an osteolytic lesion of the ascending ramus. Biopsy revealed adenocarcinoma of obscure origin. Staining of the specimen with a monoclonal antibody specific to colon carcinoma revealed its origin. On subsequent examinations, a primary tumor in the rectosigmoid region with extensive lung, liver and skeletal metastases were diagnosed. This unusual case of colonorectal carcinoma, presenting as a metastatic lesion of the mandible, was readily diagnosed by a novel immunohistochemical technique that utilizes highly specific monoclonal antibodies.

Adenocarcinoma↗