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At least 55 records · Page 3Linked to original sources

Tumour-associated macrophages (TAMS): disordered function, immune suppression and progressive tumour growth.

Evidence currently available suggests that in established, progressively growing solid tumours, tumour associated macrophages (TAMs) are reprogrammed to induce immune suppression of host defenses in situ, through release of specific cytokines, prostanoids and other humoral mediators. This disordered response, results in the inhibition of effective anti-cancer cell-mediated immune mechanisms. Concurrently, TAMs produce tumour growth promoting factors. The summation of this complex interplay of biological factors results in progressive tumour growth and tumour cell dissemination. A better understanding of these complex inter-relationships should form the basis of novel strategies designed to eradicate tumour cells in man and animals. These various biological aspects and processes are discussed in detail and critically evaluated in this review article.

Apoptosis↗

Qui tam litigation: "whistleblower" lawsuits.

Qui tam lawsuits are increasingly being used in the fight against fraud in the managed care environment. Brought by private individuals, called relators, on behalf of the U.S. government, the lawsuits aim to recover funds obtained through the presentment of false claims. The relator may eventually collect between 15% and 30% of the funds recovered. This article provides an overview of qui tam litigation and its role in the government's war against fraud.

Fraud↗

Clinical trial of combined hormone therapy (MAP + TAM) for metastatic breast cancer.

High dose MAP (medroxyprogesterone acetate) and TAM (tamoxifen) were administered orally to 31 postmenopausal patients with advanced breast cancer. CR (complete remission) was achieved in 1 (3%) and PR (partial remission) in 11 (32%) patients for a median duration of 12 months. The treatment was well tolerated and in no instance was interrupted because of toxicity. This study does not support the hypothesis that the combination of MAP and TAM gives better results than the single agents.

Aged↗

[Comparison of CAF plus MPA with CAF plus TAM for advanced or recurrent breast cancer--Kyushu CAFT Study Group of Advanced or Recurrent Breast Cancer].

A multi-center randomized comparison study of CAF + TAM therapy (Arm A) and CAF + MPA therapy (Arm B) in advanced or recurrent breast cancer was conducted at 37 institutions in Kyushu. Out of 119 registered cases, 114 were eligible and 76 were evaluable. The response rate was 42% (15/36) in Arm A and 58% (23/40) in Arm B. In the comparison of side effects, nausea/vomiting and anorexia were significantly less and moon face and body weight gain were significantly more in Arm B. Leucocytopenia was significantly inhibited in Arm B compared with Arm A, which indicated the myeloprotective effect of MPA. These results indicated that CAF + MPA therapy (Arm B) may be more advantageous than CAF + TAM therapy (Arm A) in advanced or recurrent breast cancer.

Antineoplastic Combined Chemotherapy Protocols↗

Effectiveness of a naturally derived insecticide, spinosad, against the pine processionary moth Thaumetopoea wilkinsoni Tams (Lepidoptera: Thaumetopoeidae) under laboratory conditions.

The pine processionary moth Thaumetopoea wilkinsoni Tams is a serious pest on pine trees in southwestern Turkey. The efficacy of a naturally derived insecticide, spinosad, on fourth-fifth instar larvae of T. wilkinsoni was studied under laboratory conditions. The product exhibited strong larvicidal activity and at doses above 5 mg litre(-1) caused > 90% mortality in the fourth-fifth larval stages of the species after 72 h. At 72 h the LD50 and LD90 values were 3.26 and 5.69 mg litre(-1) respectively. The results showed that spinosad is highly effective on T. wilkinsoni larvae.

Animals↗

Hepatotoxic effect of thioacetamide (TAM) on NADP-linked enzymes, aminotransferases and glutamate dehydrogenase.

NADP-linked dehydrogenases, glucose-6-P dehydrogenase (G 6PDH) 6-P gluconate dehydrogenase (6 PGDH), isocitrate dehydrogenase (ICDH), malate dehydrogenase decarboxylating (ME) and aminotransferases GOT and GPT were analyzed in the soluble fraction of blood free homogenates. Glutmate dehydrogenase (GDH) was assayed in the mitochondrial fraction. TAM was i.p. administered to male albino rats (50 mg/kg/day) for 28 days. enzyme activities were determined as described by Bermeyer 1965 (Methods Enzymatic Analysis. Verlag Chemie. Acad. Press).

Acetamides↗

Autologous stem cell transplantation using modified TAM or combination of triple-alkylating agents conditioning regimens as one of the post-remission treatments in patients with adult acute myeloid leukemia in first complete remission.

A total of 174 newly diagnosed adult acute myeloid leukaemia (AML) patients were treated in first complete remission (CR1) using modified TAM or a combination of triple-alkylating agents followed by autologous transplantation (AT). Cytogenetic risk groups were classified and most patients received mobilized peripheral blood stem/progenitor cells (PBSCs). The infused cell dose consisted of a median of 4.1+/-2 (range, 1.2-17.1)x 10(6)/kg CD34+ cells. With a median follow-up of 51 months (range, 5-131 months) after CR1, the estimated 5-year disease-free survival (DFS) rate was 68 (95% confidence interval (CI), 63-73%) and the event-free survival rate at 5 years was 59 (95% CI, 54-64%). AML patients other than M3 subtype, the long-term DFS rate was 76, 33% for favourable and unfavourable risk groups, respectively. In all, 40 patients had relapses (40/174, 23%) at the median 15 months after CR1 (range, 8-66 months). Overall, seven patients (4%) died in connection with AT. The infused CD34+ cell dose (P=0.0389) was associated with survival by multivariate analysis. In conclusion, two novel conditioning regimens in AT are feasible for adults with variable risk AML followed for over a 10-year period.

Acute Disease↗

Use of a cDNA recombinant for the gamma-subunit of mouse nerve growth factor to localize members of this multigene family near the TAM-1 locus on chromosome 7.

The gamma-subunit of mouse 7S nerve growth factor (gamma-NGF) is a member of a family of closely related serine proteases that includes kallikreins and tamases. We have isolated from a DBA/2J male submaxillary gland cDNA library a clone, pSM676, which codes for gamma-NGF. Sequence analysis of the clone shows that it codes for the C-terminal 138 amino acids of the protein plus 23 bases of the 3'-nontranslated portion of the message. The predicted amino acid sequence agrees with that determined by Thomas et al. (1) for the gamma-subunit of nerve growth factor from Swiss Webster mice except for the single, conservative substitution of glutamate for aspartate at amino acid 175. When used as a probe for Southern blot analysis, pSM676 hybridizes to at least twelve fragments of restricted mouse genomic DNA which correspond to several different serine protease genes. Using mouse-hamster hybrid cell lines and recombinant inbred strains of mice, we have demonstrated that all of the genes which show homology to pSM676 are located on mouse chromosome 7, clustered at or near the Tam-1 locus.

Animals↗

Purification and properties of two isozymes of gamma-glutamyltranspeptidase from Bacillus subtilis TAM-4.

Two isozymes of gamma-glutamyltranspeptidase, GGT-A and GGT-B, were purified to electrophoretic homogeneity from a culture broth of Bacillus subtilis TAM-4, which produces poly(gamma-glutamic acid) (PGA) de novo. GGT-A was composed of three subunits with molecular weights of 23,000 (I), 39,000 (II), and 40,000 (III). GGT-B was composed of two subunits with molecular weight of 22,000 (I) and 39,000 (II). The N-terminal amino acid sequences of GGT-A subunit I and GGT-B subunit I were very similar. GGT-A subunit II and GGT-B subunit II had an identical N-terminal amino acid sequence. That of GGT-A subunit III showed no similarity to the other subunits. Both GGTs had similar enzymatic properties (optimum pH and temperature: pH 8.8 and 55 degrees C) but showed a significantly different thermal stability at 55 degrees C. Both GGT-A and -B used D-gamma-glutamyl-p-nitroanilide as well as the L-isomer as the gamma-glutamyl donor and used various amino acids and peptides as the acceptor. It was also found that the PGA produced by the strain was hydrolyzed to glutamic acid by its own GGTs.

Amino Acid Sequence↗

Toxicity of essential oils extracted from Origanum onites L. and Citrus aurentium L. against the pine processionary moth, Thaumetopoea wilkinsoni Tams.

The pine processionary moth (PPM), Thaumetopoea wilkinsoni Tams. (Lepidoptera: Thaumetopoeidae), is an important forest pest in the Mediterranean area, additionally urticating hairs of the caterpillars of this species cause strong allergic reactions on skin of humans and animals. In the present study, essential oils extracted from aerial parts of Origanum onites L. and fruit peels of Citrus aurentium L. were tested at three doses (0.1, 0.5 and 1%) against 4th and 5th instar larvae of the pest. The results showed that the activities were concentration dependent. The LD50 and LD90 values were 0.288 and 0.926% for O. onites, 0.530 and 2.306% for C. aurentium, respectively.

Animals↗

Qui tam: suing physicians who make false claims.

The 1986 False Claims Act Amendments authorize private citizens to sue on behalf of the U.S. government to recover federal funds from fraudulent recipients. The "relator" receives a share of any proceeds from a successful lawsuit. Originally enacted because of defense procurement scandals, this statute also applies to federal payments for health care (for example, Medicare, Medicaid, Civilian Health and Medical Program for Uniformed Services payments; veterans benefits; and research grants). Physicians can expect qui tam litigation to increase in the future.

Financing, Government↗

When you hear that whistle blowing. How trustees can reduce the threat of "qui tam" lawsuits.

The number of qui tam--whistle-blower--lawsuits against hospitals has increased 1,500 percent in the last decade--in large part because of the high priority the government attaches to Medicare fraud and abuse. Even suits that never make it to court are financially draining and a blow to an organization's reputation. Here are some tips for protecting your hospital.

Duty to Warn↗

[Combination therapy of doxifluridine (5'-DFUR) + cyclophosphamide (CPA) + tamoxifen (TAM) for advanced or recurrent breast cancer. Joint Research Group in the Osaka Area for Combination Therapy of 5'-DFUR with Other Drugs].

Outpatients with advanced and recurrent breast cancer were treated by a combination therapy of the following drugs: doxifluridine (5'-DFUR) orally administered at a dose of 1200 mg/day; cyclophosphamide (CPA) orally given at dose of 100 mg/day; and tamoxifen (TAM) orally given at dose of 20 mg daily. 5'-DFUR and CPA were administered on consecutive days 1-14, then discontinued for 14 days. The response rate was 44.8% including five CR and eight PR out of 29 complete cases. As for response cases in terms of the subject lesions, corresponding cases were chiefly found in soft tissue and the lung. As for the response rate with or without pretreatment, cases previously treated showed a higher response rate such as 42.9% indicating that the present therapy was effective in pretreatment cases. The main side effect was leukopenia, but not so severe. Few cases with diarrhea were found. Based on the above findings, the present treatment is conceivably a highly useful therapy, on an outpatient basis, for advanced and recurrent breast cancer, especially metastatic lesions of soft tissue and the lung.

Administration, Oral↗

[A comparative study with 5'-DFUR alone or in combination with tamoxifen (TAM) or medroxyprogesterone acetate (MPA) for advanced or recurrent breast cancer].

A comparative study of 5'-DFUR 600 mg/day alone (C-arm) or in combination with TAM 30 mg/day (A-arm) or MPA 600 mg/day (B-arm) was carried out. Thirty-four patients (aged 80 or less) with no prior treatment were evaluable, and the following results were obtained. 1) Patient characteristics were similar in each treatment group and the compliance in all groups was excellent. 2) The group B response rate (70.0%) was considerably higher than that of group A (23.1%) and C (27.3%). 3) In B, the response rates in soft tissues (80.0%) and bone (71.4%) were still good. 4) Mild side effects were encountered in about 15% of each group. We confirmed that combination chemotherapy with a low dose of 5'-DFUR and MPA was effective for first line treatment of metastatic breast cancer.

Adult↗

Qui tam actions: best practices for relator's counsel.

The False Claims Act empowers the U.S. Government to identify and prosecute fraud. It does so in no small part by engaging qui tam relators who, with their attorneys, are deputized under the Act to help investigate and prosecute these cases. By combining the insight and industry-specific knowledge of the citizenry with the investigative and prosecutorial resources of the government, Congress attempted to facilitate a united front against pervasive fraud and abuse by government contractors, an aggressive effort that has borne fruit, recovering funds and protecting important federal programs. This Article proposes ways in which relators' counsel and government attorneys can work together more effectively in these cases to achieve the goals of the statute.

Cooperative Behavior↗

A concise and efficient route to 2alpha-(omega-hydroxyalkoxy)-1alpha,25-dihydroxyvi tam in D3: remarkably high affinity to vitamin D receptor.

[reaction: see text]A convenient and potentially valuable synthetic approach to the novel 2alpha-functionalized 1alpha,25-dihydroxyvitamin D3 [1alpha,25(OH)2D3] derivatives (1a-c), which are the C2-epimer of ED-71 and its analogues, has been developed. The C2alpha-modified ring A precursors (1,7-enynes 16, n = 0, 1, and 2) were constructed stereoselectively starting from D-glucose in high yield. In the synthesized 2alpha-(omega-hydroxyalkoxy)-1alpha,25(OH)2D3 derivatives, 1a and 1b showed a greater binding affinity to vitamin D receptor (VDR), up to 1.8 times that of the native hormone.

Animals↗