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Biomedical subjects

A Shani

Publications and source records attributed to A Shani.

At least 37 records · Page 2Linked to original sources
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↗
PubMed1993

The protective role of ammonium trichloro(dioxoethylene-O,O')tellurate in combination with several cytotoxic drugs acting by different mechanisms of action.

We have demonstrated previously that the immunomodulator AS101 can protect mice from acute lethal toxicity mediated by high doses of radiation or chemotherapy. The compound was shown to rescue mice from toxic effects of cyclophosphamide or 5-fluorouracil. The results presented herein demonstrate that pretreatment of mice with AS101 protects them from lethal effects of several chemotherapeutic drugs acting by distinct mechanisms. At sublethal doses, AS101 could prevent hemopoietic damage caused by the drugs. A significantly higher proportion of colony forming cells granulocyte-macrophage as well as a higher level of colony stimulating factor secretion by bone marrow (BM) cells was observed in mice pretreated with AS101 before injection of doxorubicin or cyclohexylchloroethylnitrosourea. Moreover, a significantly higher rate of survival was observed in mice injected with AS101 before treatment with lethal doses of these drugs. AS101 could also rescue BM stromal cells from damages caused by doxorubicin. We show that injection of mice with AS101 or pretreatment of BM cells with AS101 protects BM-colony forming cells granulocyte-macrophage from toxic effects of etoposide. We suggest that the protective effects of AS101 against damages caused by a variety of cytotoxic drugs may be attributed to the ability of the compound to expand the colony forming unit spleen subpopulation of early progenitors, those cells that are resistant to several DNA damaging agents and are the precursor cells essential for reconstitution of the hemopoietic system. It seems that AS101, by minimizing adverse cytotoxicity resulting from a variety of drugs, is a promising candidate for chemoimmunotherapy with cancer patients.

Adjuvants, Immunologic↗
PubMed1993

The leukocyte adherence inhibition test (LAI) in preoperative diagnosis of epithelial ovarian cancer.

One hundred two women admitted for evaluation of an adnexal mass were tested prior to surgery by the computerized tube leukocyte adherence inhibition (LAI) assay. The test was positive in 24/35 (69%) patients, diagnosed after surgery as epithelial ovarian cancer while 50/67 (75%) of those diagnosed as benign masses were negative. Only 2/38 (5%) of normal control subjects showed a false-positive result. The LAI test described in this report showed a sensitivity of 88% and a specificity of 75% in stage I ovarian cancer; thus it may be useful for early diagnosis of ovarian malignancy.

Adnexal Diseases↗
PubMed1993

An unusual presentation of adenoid cystic carcinoma of the lacrimal gland.

Adenoid cystic carcinoma of the lacrimal gland is a highly malignant tumor usually characterized by symptoms of less than 1 year's duration. Computed tomographic (CT) findings of adjacent bony erosion or focal tumor sclerosis are also suggestive. We present a 57-year-old female patient who manifested symptoms of an enlarging mass in the right lacrimal fossa for almost 3 years prior to the establishment of the diagnosis of adenoid cystic carcinoma. CT findings during those years were not supportive for malignancy. The treatment included en bloc resection of the mass and adjacent bone and radiotherapy.

Carcinoma, Adenoid Cystic↗
PubMed1993

Increased DNA repair ability after irradiation following treatment with the immunomodulator AS101.

Ammonium trichloro(dioxoethylene-o-o')tellurate (AS101) is a new synthetic compound previously described by us as being able to modulate the immune system and having minimal toxicity. Clinical trials are currently in progress with AS101 on cancer patients. AS101 has recently been found to have radioprotective effects on hemopoiesis and survival of irradiated mice when administered prior to irradiation. Radioprotection conferred by AS101 has recently been demonstrated by us to result partly from induction of progenitor cells to enter into S phase, which is assumed to be a more radioresistant phase of the cell cycle, and partly from the enhanced stimulation of CFU-S not only toward proliferation but also toward self-renewal. In the present study we demonstrate that the DNA repair processes expressing the cellular reponses associated with the restoration of the normal nucleotide sequence after damage caused to the DNA were also increased significantly after treatment with AS101. Unscheduled DNA repair synthesis was found to be significantly higher in both spleen and bone marrow cells from mice injected with AS101 compared to mice injected with PBS. DNA repair synthesis in spleen cells incubated with AS101 in vitro was also higher than that of PBS-treated cells. This was demonstrated by equilibrium alkaline cesium chloride density gradient of DNA from irradiated and nonirradiated spleen cells in the presence of hydroxyurea. In addition, using the neutral filter elution technique, we show that AS101 can both protect cells from DNA double-strand breaks (DSBs) induced by irradiation and enhance the ability of the affected cells to rejoin the DSBs. We show that extracts of splenocytes, either incubated with AS101 in vitro or obtained from mice injected with AS101, contain substantial DNA polymerase activity which is significantly higher compared to that of control treated cells. Aphidicolin, an inhibitor of DNA polymerases alpha and delta, and dideoxy-thymidine, an inhibitor of DNA polymerase beta, inhibited DNA repair synthesis of irradiated splenocytes stimulated with AS101. These results collectively indicate that AS101 confers its radioprotective effects partly by preventing the induction of DSBs induced by irradiation and partly by enhancing the ability of irradiated cells to repair their damaged DNA, probably by increasing mainly DNA polymerase activity. The understanding of the mechanism of radioprotection conferred by AS101 will enable us to use AS101 more effectively for the restoration of hemopoiesis in patients after radiation therapy or in patients suffering from overdose or accidental irradiation.

Adjuvants, Immunologic↗
PubMed1992

Pneumothorax following induction chemotherapy in patients with lung metastases: a case report and literature review.

A 29-year-old patient presented with bilateral pulmonary lesions following surgery for recurrent placental site trophoblastic tumor (PSTT). On day seven after institution of the 'EMA' regimen (etoposide, medium dose methotrexate with folinic acid rescue and actinomycin-D), complete pneumothorax occurred. Closed-system air drainage brought only transient lung expansion and subsequent talc pleurodesis was needed. During follow-up, complete regression of lung metastases was observed. A literature survey of post-chemotherapy pneumothorax in patients with lung metastases disclosed fourteen hitherto reported cases. Including the present PSTT case, non-epithelial gynecologic malignancy (3 patients) ranks second to osteogenic sarcoma (6 cases) with regard to the primary tumor involved.

Adult↗
PubMed1992

Localised deep microwave hyperthermia in the treatment of benign prostatic hyperplasia: long-term assessment.

A group of 133 patients with benign prostatic hyperplasia who were either poor operative risks or who had refused surgery underwent localised deep microwave hyperthermia, without supplementary drugs. In 59% of patients who had had an indwelling catheter, freedom from urological obstruction and satisfactory voiding were maintained for 7 years and catheterisation was not required. In patients with severe prostatic symptoms, 65% showed general improvement and satisfactory voiding for 8 years. There were no side effects. Patients who relapsed were given a second course of treatment and 75% responded positively. This positive response and the lack of side effects suggest that localised deep microwave hyperthermia may be an effective alternative to surgery in the management of high risk patients and those who are reluctant to undergo surgery.

Aged↗
PubMed1990

[Noninvasive, local microwave hyperthermia for deep-seated tumors: III. Benign prostatic hyperplasia].

Poor operative risk patients with benign prostatic hyperplasia were treated as outpatients with local hyperthermia without sedation, for 1 hour, twice weekly. As a result of the treatment it was possible in 61% to remove indwelling catheters and voiding was resumed for up to 61 months after treatment. 70% of those without indwelling catheters improved clinically and remained so for 67 months after completion of treatment. There were no side-effects or sequellae of the treatment. Because of its safety, simplicity of application and good results, it is recommended as the treatment of choice for poor operative risks.

Catheters, Indwelling↗
PubMed1990

[Screening for colorectal neoplasms].

We screened groups at high risk for colorectal neoplasms, determining the efficacy of the leukocyte adherence inhibition test (LAI) for early detection, in comparison with that of the fecal occult blood (Hemoccult) test and sigmoidoscopy or colonoscopy. Those screened included 549 first-degree relatives of patients with colorectal cancer, 190 patients with a past history of colorectal adenoma or carcinoma and 67 with a past history of breast or gynecological cancer or inflammatory bowel disease. 146 normal volunteers served as controls. In 782 of those fully screened during a 3-year period, 121 had adenomas (15.5%) and 5 had invasive cancer (0.6%). The LAI test was positive in 21% of those at high risk and in 7.5% of the controls. The hemoccult test was positive in only 4.8%, but in 1/3 of them neoplasms were found. This predictive value of 33% compares with only 16% for the LAI test. That most of the neoplasms found were adenomas and not invasive cancer may be due to the relative youth of most of those screened. We conclude that the groups studied were indeed at high risk. The LAI test is not sensitive enough to identify benign adenomas but might serve as another risk-market for colorectal neoplasms. Long-term follow-up of those at high-risk with positive LAI tests may prove that we have identified a subgroup truly at risk.

Adenoma↗
PubMed1990

Immunologic effects of AS101 in the treatment of cancer patients.

AS101 [ammonium trichloro(O,O'-dioxyethylene)tellurate] is a new immunomodulator previously shown to stimulate the production of different cytokines in vitro and in vivo. We report here our results of a phase I clinical trial conducted on 47 cancer patients with advanced malignancies. AS101 was administered intravenously at escalating doses from 1 to 10 mg/m2, twice or thrice a week. The maximal tolerated dose has not yet been determined. However, significant immunologic responses were noted at dose levels of 1-3 mg/m2 administered three times a week. At these doses statistically significant rises in gamma-interferon, natural killer cell activity, tumor necrosis factor and interleukin-2 (IL-2) levels as well as the expression of IL-2 receptors were noted. In most of the immunologic parameters the maximal response was seen at 3 mg/m2. Throughout the study toxicity was minimal. In view of these results phase II studies are currently being initiated.

Adjuvants, Immunologic↗
PubMed1989

Endolymphatic stromal myosis (endometrial low-grade stromal sarcoma) presenting with hematuria: a diagnostic challenge.

In this case of a 41-year-old white woman who presented with hematuria, the diagnosis of metastatic endolymphatic stromal myosis (ESM) in the urinary bladder was reached on the basis of the histologic pattern and with the aid of intermediate filament typing. In the hysterectomy specimen the tumor foci of ESM were of minute size. To the best of our knowledge, this is the first report of such an unusual clinical presentation of this lesion.

Adult↗
PubMed1989

Prevalence of Candida albicans in denture wearers in an Israeli geriatric hospital.

Thirty-seven patients wearing complete dentures were investigated for Candida albicans. Twenty-five of the patients suffered from denture stomatitis and twelve had clinically normal mucosa. Candida albicans was isolated and identified from Sabouraud dextrose agar culture medium models constructed from impressions of the maxilla and from the upper dentures. The presence of Candida albicans was demonstrated in all denture wearers suffering from denture stomatitis and in 82% of denture wearers in a control group. A higher concentration of Candida was found in the denture stomatitis group. Large quantities of Candida resided in the denture base and not in the palate. Candida was also found in the denture base in areas not related to the lesion. The concentration of Candida was related to denture cleanliness.

Aged↗
PubMed1989

Anti-tumor immunity in breast cancer evaluated by a computerized tube leukocyte adherence inhibition (LAI) assay.

Seventy-four women admitted for breast biopsy were monitored before surgery for anti-tumor cell-mediated immunity using a computerized tube leukocyte adherence inhibition (LAI) assay. Spent medium from breast, lung and colon adenocarcinoma cell lines was used as the source of organ-specific neoantigens for standardization of the assay. Peripheral blood leukocytes from 25/40 (62.5%) patients diagnosed after surgery as breast cancer responded to spent medium with a positive non-adherence index (NAI). A positive NAI was inversely related to tumor mass because only 7/18 (38.8%) of those with Stage III or IV had a positive NAI; while 18/22 (81.8%) of those with Stage I or II were positive. Cross-reactive antigenicity was not observed when spent medium from breast cancer was incubated with leukocytes from patients with several other solid tumors nor when leukocytes from breast cancer patients were incubated with spent medium from lung or colon carcinoma cell lines. The antigenic material in the spent medium appears to be an organ-specific neoantigen because only 1/34 patients with benign breast disease had a positive NAI and all normal healthy control individuals were negative. The results of this study show that spent medium of a breast carcinoma cell line is more reliable than crude cancer extracts for use in LAI to detect specific anti-tumor cellular immune responses. The improved method presented in this report can be a useful tool in the early diagnosis of breast cancer and for monitoring of patients with this disease.

Adult↗
PubMed1989

Limited value of leukocyte adherence inhibition in screening for colorectal neoplasia in high-risk groups.

A study of 191 screenees at high risk for colorectal neoplasm was undertaken to evaluate the value of the leukocyte adherence inhibition (LAI) test in detecting colorectal neoplasms. All screenees underwent total colonoscopy and LAI test. Results show that 94/191 (49.2%) screenees had neoplasms. Overall LAI positivity was 18.3% (35/191), which was highly significant, versus an asymptomatic comparison group (7.5%, 11/146). LAI test sensitivity, specificity, and positive and negative predictive values were, respectively, 19.8, 82.7, 45.7, and 58.5%. In this study the LAI test was not found to be a sensitive screening test for colorectal neoplasms. However, as the LAI test result was a significant finding within the study group, it may possibly be a risk factor and identify a subgroup that will require careful prospective evaluation.

Adult↗