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Biomedical subjects

A Shani

Publications and source records attributed to A Shani.

At least 19 recordsLinked to original sources
PubMed2001

Evasion of mating disruption in Ephestia cautella (Walker) by increased pheromone production relative to that of undisrupted populations.

The effect of applying high dosages of pheromone for continuous disruption of mating on sex pheromone production, fecundity, and life span was studied in inbred pairs of the almond moth (Ephestia cautella) mated in glass jars. Two experiments were conducted for six and nine consecutive generations of disruption, respectively, with a pheromone mixture (2.2-2.4mg/jar in the first experiment and 10mg/jar in the second experiment) composed of two components, (Z,E)-9,12-tetradecadienyl acetate (D) and (Z)-9-tetradecenyl acetate (M), in various proportions. In the first experiment pheromone emission decreased considerably in the first generation of disruption, an average of 35% lower in the control F(1) females and 47% lower amount in females of the disrupted population (exposed to an excessive pheromone dose) as compared with the amount recorded in parental (P) females (1252+/-84pg). The reduction in pheromone emission continued in the two treatment groups, by an average of 92 pg/generation in the control and 64pg/generation under disruption until F(5). The same trend of reduction of pheromone production (as measured in gland extract) was also detected in the second experiment, with leveling off at 2.5+/-2.3 and 2.7+/-1.6ng/gland in F(7) and F(8), respectively, for the control population, and 5.7+/-5.6 and 5.9+/-5.7ng/gland in F(7) and F(8), respectively, for the disrupted population (initial pheromone level in P was 33.8+/-18.7ng/gland). The confinement of the pairs in closed jars was probably the major cause for the reduction in pheromone production besides inbreeding. The higher pheromone titer in the disrupted population relative to that in the control population may represent an evasion of the pressure of mating disruption caused by selection. The mean number of progeny (per jar) gradually decreased in successive generations in both the control and disruption treatments, but no significant difference was found between the number of progeny averaged over all the generations in the two treatments. For a pheromone blend having the average composition of D:M=77:23 in the first experiment, there was a small but significant increase in the life span among disrupted mated and unmated males (10.5 and 10.2 days, respectively) and among disrupted mated and unmated females (7.7 and 11.0 days) as compared with the respective non-disrupted control groups (9.3 and 6.5 days for the males and 6.7 and 8.6 days for the females).

Journal Article↗
PubMed2001

CMF (cyclophosphamide, methotrexate, 5-fluorouracil) versus cnf (cyclophosphamide, mitoxantrone, 5-fluorouracil) as adjuvant chemotherapy for stage II lymph-node positive breast cancer: a phase III randomized multicenter study.

A multicenter phase III randomized study compared the efficacies of two adjuvant polychemotherapeutic regimens in 145 patients with stage II node-positive breast cancer. The standard chemotherapy combination, CMF (cyclophosphamide, methotrexate, 5-fluorouracil), was administered to 77 women. The experimental protocol, CNF (cyclophosphamide, mitoxantrone, 5-FU), in which mitoxantrone (Novantrone) replaced methotrexate, was given to 68 patients. Follow-up of the 145 patients by six participating hospitals showed no statistically significant difference (p = 0.6) between the two treatment regimens during a median follow-up of 4.5 years in terms of overall survival. There was, however, a significant advantage (p = 0.04) in the disease-free survival for those receiving mitoxantrone (mean survival 4.4 years for CNF versus 2.7 years for CMF). Toxic side effects associated with CNF (particularly alopecia and myelotoxicity) were relatively more frequent but acceptable and did not lead to dose reduction. In light of its association with improved disease-free survival in this study, larger studies should be undertaken on the role of mitoxantrone as adjuvant treatment in stage II breast cancer.

Adult↗
PubMed2000

Synergistic anti-tumoral effect of paclitaxel (Taxol)+AS101 in a murine model of B16 melanoma: association with ras-dependent signal-transduction pathways.

Optimal doses of paclitaxel (Taxol) combined with the immunomodulator AS101, previously shown to have anti-tumoral effects, administered to B16 melanoma-bearing mice decreased tumor volume and resulted in over 60% cure. Paclitaxel+AS101 directly inhibited the clonogenicity of B16 melanoma cells in a synergistic, dose-dependent manner. We suggest that this results from both reduced paclitaxel-induced bone marrow toxicity and induction of differential signal-transduction pathways, which lead to apoptosis of tumor cells. Paclitaxel+AS101 synergistically activated c-raf-1 and MAPK ERK1 and ERK2. This activation was essential for the synergistic induction of p21(waf) protein. Cell-cycle analysis of B16 cells treated with both compounds revealed an increased accumulation in G(2)M, though AS101 alone produced significant G(1) arrest. These activities were ras-dependent. AS101+paclitaxel induced significant synergistic phosphorylation (inactivation) of the anti-apoptotic protein Bcl-2. Whereas phosphorylation of Bcl-2 by paclitaxel was raf-dependent only, the synergistic effect of both compounds together was ras-, raf- and MAPK-dependent. No effect of the combined treatment on Bax protein expression was observed. We suggest that AS101 renders more cells susceptible to Bcl-2 phosphorylation by paclitaxel, possibly by increasing the accumulation of paclitaxel-induced cells in G(2)M. Exposure of B16 cells to clinically achievable concentrations of paclitaxel+AS101 increased the rate of apoptosis of treated cells. Apoptosis induced by AS101 alone was both raf- and MAPK-dependent, while that induced by paclitaxel was raf-dependent only.

Animals↗
PubMed1999

Conservative treatment of adenocarcinoma of the endometrium in young patients. Is it appropriate?

Few reports have suggested that nulliparous young patients with endometrial cancer may be treated conservatively to preserve fertility. We present a young nulliparous woman with a well differentiated adenocarcinoma of the endometrium treated with progestins. Since she did not respond, a definite operation was performed revealing involvement of the uterine isthmus, thus necessitating adjuvant radiotherapy.

Adenocarcinoma↗
PubMed1999

Diagnostic dilemmas and current therapy of Fallopian tube cancer.

Primary tubal cancer, unlike ovarian cancer, is not routinely suspected preoperatively, and thus diagnosis and therapy are delayed. We have recently encountered two cases in which primary Fallopian tube cancer masqueraded as other lesions. One presented as a pelvic inflammatory process, the second as cervical cancer. Primary Fallopian cancer should be suspected by the clinician, even if the presenting symptoms are atypical. Chemotherapy with taxol and cisplatin was instituted following debulking surgery.

Adenocarcinoma↗
PubMed1998

The role of the soluble p53 antigen and its autoantibodies as markers for diagnosis of colon cancer: a comparative study.

The role of various serological tumor markers, p53 soluble antigen and its autoantibodies, was evaluated for the detection of colon cancer in humans. An HPLC technique was used to measure serum levels of both forms of p53 protein after their partial isolation on gel fiberglass affinity chromatography columns. Tumor-associated proteins (TAP) in the form of either antigens or autoantibodies were about 4% of the total protein isolated from the serum of colon cancer patients. The absolute amount of each of the two types of TAP was also similar: 14.69 2.88 and 18.29 3.85 mg ml-1, respectively. The amount of p53 autoantibodies was higher than those of p53 antigen, but the difference was not significant: 9.35 3.48 and 6. 19 3.87 mg/ml, respectively (p>0.05). A good correlation was found between the total amount of tumor-associated antigens (TAA) and the amount of p53 antigen (r=0.69), total amount of IgG and the amount of p53 autoantibodies (r=0.46), and between both forms of p53 protein (r=0.46). A high coefficient of regression was found between the total amount of TAA and the amount of p53 antigen (b=2.4). Relationships between Duke's stage in colon cancer and the serum levels of p53 protein were weak: 0.33 and -0.32 for p53 antigen and its autoantibodies, respectively. Serum determination of p53 autoantibodies has no advantage over the determination of p53 antigen. Both forms of p53 protein can be isolated with extremely high accuracy for the pathological diagnosis of cancer (87-93%). Specificity of the method was proved using of commercial p53 PAb OD1: the GFG columns with this antibody were able to isolate the same proteins which were isolated by GFG columns with anti-p53 IgG. Moreover, the isolation of p53 protein was performed with higher effectiveness using the GFG columns with entrapped anti-p53 IgG than those columns with commercial DO1 PAb.

Autoantibodies↗
PubMed1997

Subcutaneous, omentum and tumor fatty acid composition, and serum insulin status in patients with benign or cancerous ovarian or endometrial tumors. Do tumors preferentially utilize polyunsaturated fatty acids?

The relationships between the fatty acid composition of cancerous endometrium and ovary, and peripheral adipose tissues were studied in Israeli Jewish women, and are presented together since no differences were shown between them. The results suggest a mobilization of linoleic acid from subcutaneous and omental depots and its incorporation into tumors accompanied by a high degree of desaturation. High blood insulin concentrations characterized patients with stage I and II disease, and low concentrations characterized patients with advanced degrees of malignancy.

Adipose Tissue↗
PubMed1996

Predominance of TH1 response in tumor-bearing mice and cancer patients treated with AS101.

BACKGROUND: Several studies have recently suggested that the immune response to malignant growths is regulated by distinct patterns of type 2 cytokine production. These cytokines, regulating the cytotoxic T-lymphocyte response in patients with advanced cancers, may be associated with disease progression. Evidence suggests that the T Helper 1 (TH1) and T Helper 2 (TH2) types of reaction are reciprocally regulated in vivo. The immunomodulator AS101 (ammonium trichloro[dioxoethylene-O,O']tellurate) was found to stimulate mouse and human cells to proliferate and secrete a variety of cytokines. Clinical trials using AS101 on cancer patients are now in progress. PURPOSE: The aim of this study was to evaluate the ability of AS101 to modulate TH1 and TH2 responses in tumor-bearing mice and in patients with advanced cancer. In addition, we investigated the association between the predominance of each type of response with the antitumoral effects of AS101. METHODS: Mice into which Lewis lung carcinoma (3LL) had been transplanted (n = 221) and cancer patients (n = 13) were treated with AS101 on alternate days, at 10 micrograms/mouse intraperitoneally, or for the patients, at 3 mg/m2 intravenously. The types were sarcoma, melanoma, and colon, lung, ovarian, and renal cancers. Cytokine levels were determined by immunoassay kits and compared with the paired Student's t test: in mice, they were tested in spleen cell supernatants; in humans, in sera and mononuclear cell supernatants. The chi-squared test was used to compare tumor volumes. All P values represent two-sided tests of statistical significance. RESULTS: Our results show that treatment of mice and patients with AS101 results in a clear predominance in TH1 responses, with a concomitant decrease in the TH2-type response. This was reflected by a significant enhancement in interleukin 2 (IL-2) and interferon gamma (IFN gamma) levels (P < .01) paralleled by a substantial decrease in IL-4 and IL-10 (P < .01). Moreover, the concentration of IL-12 was significantly increased (P < .01) in AS101-treated patients who also showed enhanced levels of natural and lymphokine-activated killer cell-mediated cytotoxicity. The statistically significant increases in IL-2 and IFN gamma levels, paralleled by the pronounced decrease in IL-4 and IL-10 in the AS101-treated mice, were associated with its antitumoral effects. In addition, systemic cotreatment of 3LL-transplanted mice with AS101 and anti-IL-12 antibodies partly abrogated the antitumoral effect of AS101. CONCLUSIONS: Immunotherapy with AS101 enhances TH1 function while interfering with the TH2 response. This TH1 trend may be related to the antitumor effects of AS101. IMPLICATIONS: Isolation and characterization of a distinct cytokine pattern in patients with advanced cancer treated with AS101 may contribute to the development of intervention strategies using this compound.

Adjuvants, Immunologic↗
PubMed1996

The antitumoral effect of the immunomodulator AS101 and paclitaxel (Taxol) in a murine model of lung adenocarcinoma.

The immunomodulator ammonium trichloro(dioxyethylene-0-0')tellurate (AS101) has been shown to possess antitumoral properties in several murine models. In the present study, we demonstrate a synergistic in vivo antitumor effect of AS101 and Taxol against early stage Madison 109 lung adenocarcinoma. Treatment with optimal doses of Taxol (25 and 17 mg/kg) and AS101 (0.5 mg/kg) resulted in 66.6 and 43.3% cures. We propose that the antitumor effect is the result of both a direct and indirect effect of the drugs on tumor cells. AS101 and Taxol directly inhibited clonogenicity of M109 cells in a synergistic dose-dependent manner. Exposure of M109 cells to clinically achievable concentrations of Taxol and AS101 produced a synergistic internucleosomal DNA fragmentation associated with programmed cell death. We suggest that AS101 renders tumor cells more susceptible to chemotherapy in general and to Taxol in particular, partly by increasing the wild-type p53 protein expression that is required for efficient execution of the death program. Moreover, we demonstrate a synergistic effect of AS101 and Taxol in increasing the tumoricidal activity of macrophages. This activity is produced by nitric oxide secretion. The synergistic antitumoral effects of AS101 and Taxol were partly ablated both in vitro and in vivo by inhibition of nitric oxide synthase. These findings indicate that AS101 in combination with Taxol may be a promising antitumor drug, and illustrate the mechanism of action of both drugs when acting synergistically. Phase II clinical trials have been initiated using AS101 in combination with Taxol.

Adenocarcinoma↗
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

(Z,E)-alpha-farnesene--an electroantennogram-active component of Maladera matrida volatiles.

It has previously been shown in field-trapping experiments and laboratory olfactometer bioassays that virgin females of Maladera matrida Argaman (Coleoptera, Scarabaeidae) and their volatiles, both in the presence of food (cut peanut leaves), are efficient attractants for M. matrida males and females. In this study GC-EAD experiments using male antennae and GC-MS experiments revealed that (Z,E)-alpha-farnesene is an active component of M. matrida female volatiles. The identification and quantitive electrophysiological responses (EAG) of synthetic (Z,E)-alpha-farnesene were obtained with male and female antennae. It was also shown that (Z,E)-alpha-farnesene is not a component of the plant volatiles that serve as synergistic components of the mixture of attractants or of the source of food for M. matrida.

Animals↗
PubMed1996

Hyperestrogenemia and presence of estrogen receptors associated with an epithelial ovarian tumor of low malignant potential.

An 80-year-old woman presented with breast congestion, tenderness and pain. Mammography was normal. Circulating estradiol was markedly elevated, while LH and FSH were low. Pelvic examination and imaging revealed an ovarian mass which was extirpated during total abdominal hysterectomy and bilateral salpingo-oophorectomy. Histopathology revealed an ovarian mucinous cystadenocarcinoma of low malignant potential, stage 1. The tumor was positively stained for estrogen receptors. Estradiol levels returned to normal post-operatively, with a corresponding adjustment of LH/FSH. Possible autocrine steroid production is discussed.

Aged↗
PubMed1996

Comparative study of the role of serum levels of p53 antigen and its tumor cell concentration in colon cancer detection.

The role of serum levels of p53 antigen in detection of colon cancer was studied in different groups of cancer and noncancer patients and was compared with the results of immunohistochemical analyses. The p53 antigen was isolated from the human serum as a cytoplasmic fraction using the recently described new type of columns for affinity chromatography, gel fiberglass columns (Zusman and Zusman, 1995). Its concentration was detected by high performance liquid chromatography. The serum level of the p53 antigen significantly increased in cancer patients (3.6 mg ml(-1)) as compared to its concentration in patients with benign tumors (1.7 mg ml(-1)) or in patients with noncancer disorders (0.49 mg ml(-1)), and this was found to be a result of higher concentration of p53 protein in tumor cells. Coefficient of correlation between cellular concentration of p53 protein and its serum level was 0.44 in noncancer lesions and 0.48 in cancer patients. Serum levels of p53 antigen was shown to be highly active either in patients with noncancer lesions or in patients with cancer (r = 0.46 and 0.51 respectively), whereas the cell determination of p53 protein was effective only among noncancer patients (r = 0.61) but not in cancer patients (r = 0.22). The findings suggests that serum determination of p53 antigen can perhaps reveal this oncoprotein already in the early stages of cancer or even predict the putative development of cancer. The possibility to use the serum-levels of p53 antigen in the follow up patients with chronic diseases and to detect transformation of these diseases into cancer, or monitoring former cancer patients in order to detect as early as possible the incidence of recurrent cancer is discussed.

Antigens, Neoplasm↗
PubMed1995

Induction of acute phase proteins in mice and humans by treatment with AS101, an immunomodulator with radioprotective properties.

AS101 (ammonium trichloro(dioxyethylene-0,0')tellurate) is a new synthetic compound previously described by us as having immunomodulating properties and minimal toxicity. Phase II clinical trials are currently in progress with AS101 on cancer patients. AS101 has been recently found to have both radioprotective and chemoprotective effects on hemopoiesis of irradiated mice or mice treated with various chemotherapeutic drugs. The present research was designed to study the in vivo induction of liver acute phase proteins secretion in mice or patients treated with AS101. Induction of these proteins, some of which have the capacity to scavenge free radicals, may contribute to radioprotection. We present evidence that treatment with the immunomodulator AS101 increases production of a variety of acute phase proteins. We demonstrate a significant elevation of serum amyloid A (SAA) in sera of treated mice, as well as an increase in SAA, factor B and ceruloplasmin in sera of patients treated with AS101. The same AS101 treatment was shown to decrease the amount of the negative acute phase protein, albumin. In addition we show that IL-1, IL-6 and TNF-alpha are important mediators of changes in SAA concentrations induced by AS101. Abrogation of SAA production in AS101 treated mice by any one of the anti IL-1R, IL-6R or TNF-alpha antibodies indicates that at least in mice, SAA production is not controlled by a single extracellular signal, but rather it is regulated, at the least, by all three cytokines in various combinations. A better understanding of the mechanism by which AS101 confers radioprotection will enable us to use it more effectively in the restoration of hemopoiesis in patients following radiation or suffering from overdose or accidental radiation.

Acute-Phase Proteins↗
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

Insulin and glucose status, tissue and plasma lipids in patients with tumours of the ovary or endometrium: possible dietary implications.

The relationship between tumour growth, insulin status, blood lipids and adipose linoleic acid (LA, reflecting long-term LA intake) was studied in 19 Jewish women suffering from early and advanced stages (ES and AS) of ovarian and endometrial tumours. Blood insulin in patients with ES tumours was four times higher than the control value in cancer-free subjects, but fell to normal levels at AS and after ES surgery (PES). Tumours and abdominal adipose tissue (AAT) had 4-6 and 1.4-1.7 times as much insulin as non-cancerous control organs. Serum total cholesterol (CHOL) and LDL-cholesterol were high at ES, dropped below normal at AS, but normalised at PES, while HDL-cholesterol increased after ES surgery. Linoleic acid in subcutaneous adipose tissue (SAT) was high in controls (26.4 + 1.5% of total fatty acids), but lower in cancer patients (20.5 + 3.7%, P < 0.05), while palmitic acid showed the opposite change. The results suggest mobilisation of glucose, cholesterol and linoleic acid for the supply of energy and structural lipids to rapidly multiplying tumour cells and possibly for prostaglandin synthesis. They also raise the question of whether the high linoleic acid intake by the Jewish population in Israel predisposes individuals to tumour development.

Adipose Tissue↗
PubMed1994

Human imprinted genes as oncodevelopmental markers.

Imprinted genes mediate unique maternal or paternal genetic roles and their function is essential in prenatal development. The reciprocally imprinted human insulin-like growth factor 2 (IGF2) and H19 genes are expressed during embryonal life, also in the placenta, and are downregulated postnatally. They reexpress in pediatric tumors (e.g. Wilms' tumor) and in inborn developmental syndromes predisposing to such tumors (e.g., Beckwith-Wiedemann syndrome). H19 (RNA transcripts) and IGF2 are manifested in Wilms' tumor, rhabdomyosarcoma, immature ovarian teratoma and gestational trophoblastic diseases. We have found that in the placenta and in urothelial carcinoma, H19 expression reflects the degree of invasiveness. These genes, displaying a tissue-specific oncofetal pattern of expression, are, therefore, tumor markers.

Beckwith-Wiedemann Syndrome↗