Isolation, stability, and characteristics of high-pressure superdormant Bacillus subtilis spores.

Bacterial spores are a major challenge in industrial decontamination processes owing to their extreme resistance. High-pressure (HP) of 150 MPa at 37 °C can trigger the germination of spores, making them lose their extreme resistance. Once their resistance is lost, germinated spores can easily be inactivated by a mild decontamination step.

Biocompatibility of Amine-Functionalized Silica Nanoparticles: The Role of Surface Coverage.

Here, amorphous silica nanoparticles (NPs), one of the most abundant nanomaterials, are used as an example to illustrate the utmost importance of surface coverage by functional groups which critically determines biocompatibility. Silica NPs are functionalized with increasing amounts of amino groups, and the number of surface exposed groups is quantified and characterized by detailed NMR and fluorescamine binding studies. Subsequent biocompatibility studies in the absence of serum demonstrate that, irrespective of surface modification, both plain and amine-modified silica NPs trigger cell death in RAW 264.

Sequence and functional characterization of the terminal exon of the human insulin receptor gene.

We present 5.1 kb of the 3' noncoding region sequence of the human insulin receptor gene and identification of four functional polyadenylation domains responsible for 3'-end processing of the 5.4, 6.

Dexamethasone mediated stabilization of insulin receptor mRNA.

To determine the mechanism of glucocorticoid mediated enhancement of insulin receptor (IR) gene expression, we cotransfected a glucocorticoid receptor expression vector and a plasmid containing a reporter gene driven by an MMTV or IR promoter into COS 7 cells. Dexamethasone (Dex) increased MMTV promoter activity by 100% but had no effect on IR promoter activity. In the glucocorticoid responsive breast cancer cell line, MCF-7, Dex increased IR mRNA by 60%, and increased the IR mRNA half-life from approximately 6hrs to > 24 hrs.

The results of modified use of chemotherapy for patients with metastatic breast cancer.

We investigated whether modifying standard chemotherapy with 5-fluorouracil, doxorubicin and cyclophosphamide (FAC) could improve the outcome of patients with advanced breast carcinoma. We changed the conventional FAC treatment as follows: firstly, we administered oestrogens during the delivery of chemotherapy. Secondly, we administered 5-fluorouracil by continuous infusion.

The clonogenic growth of advanced breast tumour lesions adds no value to that of established clinical prognosticators for survival.

We measured the clonogenic growth of 110 breast cancer samples obtained from 107 patients with advanced disease. We determined clonogenicity under conventional conditions and under conditions supplemented with growth factors and hormones that target breast tissue. After a median follow-up period of 6 years we analyzed our data to determine if and to what degree clonogenic growth of metastatic breast tumours was related to the survival of patients.

Nuclear protein-binding analysis of a GC-rich insulin-receptor promoter regulatory region.

We previously demonstrated that activation of the insulin-receptor promoter occurs between Xho I and HindIII restriction enzyme sites located 877 and 578 bp upstream, respectively, from the translational initiation site. Deletion mutants 5' of this promoter region were constructed with the reporter gene, CAT, and transiently transfected into HepG2 and MCF-7 cells. This study demonstrated that most of the promoter activity could be localized to a 40-bp region between -618 and -578.

Regulation of insulin receptor gene expression. Cell cycle-mediated effects on insulin receptor mRNA stability.

Posttranscriptional mechanisms play important roles in insulin receptor gene regulation; variability in cellular insulin receptor number and the growth arrest-mediated increases in insulin receptor mRNA are secondary to changes in insulin receptor mRNA stability. Therefore, further characterization of the pathways and kinetics of insulin receptor mRNA degradation were investigated. The insulin receptor mRNA in the insulin receptor-rich Hep G2 cells is more stable compared with the insulin receptor-sparse MCF-7 cells.

Adjuvant therapy with escalating doses of doxorubicin and cyclophosphamide with or without leukocyte alpha-interferon for stage II or III breast cancer.

Purpose: A prospective study in breast cancer patients was undertaken to determine whether escalating doses of doxorubicin and cyclophosphamide would result in a higher fraction of patients free of disease, and to evaluate the role of leukocyte alpha-interferon.

Patients And Methods: Between 1982 and 1986, 319 consecutive patients with stage II or III breast cancer with one or more positive nodes were assigned randomly to receive adjuvant chemotherapy that consisted of escalating doses of doxorubicin and cyclophosphamide in combination with vincristine and prednisone or the same chemotherapy regimen followed by 1 year of leukocyte alpha-interferon. Doxorubicin was administered by 72-hour continuous infusion through a central venous catheter (maximum total cumulative dose, 430 mg/m2).

Clinical course of patients with breast cancer with ten or more positive nodes who were treated with doxorubicin-containing adjuvant therapy.

Between 1974 and 1986, 283 patients with ten or more positive nodes were treated in four prospective trials using doxorubicin-containing adjuvant chemotherapy. At a median follow-up of 92 months, 182 patients had had a recurrence, and 158 died. An estimated 41% and 37% were disease-free at 5 and 7 years, respectively.

Is chemotherapy effective in reducing the local failure rate in patients with operable breast cancer?

To evaluate the role of chemotherapy in local control of primary breast cancer, the incidence of local failure was evaluated in 768 patients treated with surgery and adjuvant, combination chemotherapy that contained fluorouracil, doxorubicin, and cyclophosphamide (FAC) at our institute between 1974 and 1982. Of these patients, 429 received postoperative irradiation (XRT) before adjuvant therapy. A group of 178 historical control patients had mastectomies and received irradiation after surgery without chemotherapy.

Inflammatory carcinoma of the breast: results of a combined-modality approach--M.D. Anderson Cancer Center experience.

A total of 106 patients with inflammatory carcinoma of the breast underwent combined-modality treatment consisting of doxorubicin-containing chemotherapy. All patients received three cycles of 5-fluorouracil, doxorubicin, and cyclophosphamide (FAC) before local therapy. From 1974 to 1977 (group A), primary radiotherapy was the local treatment modality and chemotherapy was given for a total of 24 months.

Sequential cyclic combined hormonal therapy for metastatic breast cancer.

Thirty postmenopausal patients who had evaluable estrogen receptor-positive or unknown metastatic breast cancer were treated with cyclic sequential combined hormonal therapy consisting of 50 micrograms of ethinylestradiol orally daily for 7 days followed by 400 mg of medroxyprogesterone acetate orally daily for 21 days, followed in turn by 7 days of rest. Cyclic administration was continued until progressive disease was detected. Patients who had had one previous chemotherapy regimen were included, but 63% of patients were previously untreated.

Predictors of hormone response for patients with ER-unknown breast tumours.

Characteristics of cells that are associated with the hormonal dependence of tumours are described, and it is shown that clonogenicity and hormone-induced proliferative response of breast tumours are as good markers of hormonal dependence as is oestrogen receptor. Thus tumours that formed less than 150 colonies per 500,000 cells seeded and that increased their proliferative activity 1.8-fold or more in response to hormones were the tumours that were likely to respond to endocrine treatments, whereas all other tumours were likely to be refractory to endocrine treatments.

Decreased cardiac toxicity of doxorubicin administered by continuous intravenous infusion in combination chemotherapy for metastatic breast carcinoma.

Two hundred and seventy-four consecutive patients with measurable metastatic breast cancer, without prior exposure to cytotoxic agents were treated with tamoxifen, 5-fluorouracil, doxorubicin, and cyclophosphamide (FAC). The initial 133 patients received doxorubicin by bolus IV administration and for the next group of 141 patients doxorubicin was administered via a central venous catheter over a 48-hour (79 patients) or 96-hour (62 patients) continuous infusion schedule. Patients treated with bolus doxorubicin had this agent discontinued usually when 450 mg/m2 were reached; for patients in the infusion group treatment was continued until evidence of progressive disease or clinical or subclinical cardiac dysfunction developed.

Management of stage III primary breast cancer with primary chemotherapy, surgery, and radiation therapy.

One hundred seventy-four evaluable patients with noninflammatory Stage III (both operable and inoperable) breast cancer were treated with a combined modality strategy between 1974 and 1985. All patients received combination chemotherapy with 5-fluorouracil, Adriamycin (doxorubicin), and cyclophosphamide (FAC) as their initial form of therapy. After three cycles of chemotherapy, local treatment in the form of a total mastectomy with axillary dissection, or radiotherapy, or both, was completed.

Sequential multiagent chemotherapy incorporating cisplatin, doxorubicin, and cyclophosphamide in the treatment of metastatic breast cancer.

Forty-three consecutive patients with metastatic breast cancer and clearly measurable disease were treated with sequential multiagent chemotherapy. Therapy consisted of the administration in fixed sequence of cisplatin, doxorubicin, and cyclophosphamide (PAC) (four cycles), vinblastine, doxorubicin, and dexamethasone (VAD) (six cycles), and VP-16, methotrexate, and 5-fluorouracil (VMF) (six cycles). At the conclusion of 16 cycles of chemotherapy, all treatment was stopped.

Adjuvant therapy of breast cancer with or without additional treatment with alternate drugs.

Three hundred ten patients with Stage II or Stage III breast cancer were entered on an adjuvant protocol consisting of a combination of 5-fluorouracil, doxorubicin, cyclophosphamide, vincristine, and prednisone (FACVP). In the second phase of the study, patients with estrogen receptor-negative tumors received sequential courses of methotrexate and vinblastine. Other patients, who were estrogen receptor-positive or unknown, were randomized to receive either tamoxifen alone or tamoxifen plus methotrexate and vinblastine.

Cisplatin in combination with continuous infusion vinblastine for refractory breast cancer.

We assessed antitumor activity and toxic effects of cisplatin and 5-day continuous infusion vinblastine in 25 evaluable patients with metastatic breast carcinoma refractory to one or more chemotherapeutic regimens. We administered cisplatin at 70 mg/m2 i.v.

Chemoresistance is not a cause of the apparent failure of adjuvant chemotherapy in postmenopausal women.

Chemotherapeutic regimens used for the adjuvant treatment of breast carcinoma are less effective when applied to postmenopausal women than when applied to premenopausal women. Differences in growth fraction or altered chemosensitivity of tumors are potential causes of the differential effects of chemotherapy in younger and older patients. We have attempted to identify the presence of these putative causes by measuring size of clonogenic cell fraction and drug sensitivity of progenitor cells on the tumors from pre- and postmenopausal women.

Phase II evaluation of Ly156758 in metastatic breast cancer.

Fourteen patients with disseminated breast cancer with primary or secondary resistance to tamoxifen were treated with LY156758. There were no complete or partial responses and 1 patient showed a minor response. These data illustrate that LY156758 did not have significant antitumor activity in patients previously treated with tamoxifen therapy.