Coherent molecular optics using ultracold sodium dimers.

Coherent molecular optics is performed using two-photon Bragg scattering. Molecules were produced by sweeping an atomic Bose-Einstein condensate through a Feshbach resonance. The spectral width of the molecular Bragg resonance corresponded to an instantaneous temperature of 20 nK, indicating that atomic coherence was transferred directly to the molecules. An autocorrelating interference technique was used to observe the quadratic spatial dependence of the phase of an expanding molecular cloud. Finally, atoms initially prepared in two momentum states were observed to cross pair with one another, forming molecules in a third momentum state. This process is analogous to sum-frequency generation in optics.

Communication about the ending of anticancer treatment and transition to palliative care.

BACKGROUND: Communication about the ending of anticancer treatment and transition to palliative care is a difficult task for oncologists. The primary aims of this study were to clarify family-reported degree of emotional distress and the necessity for improvement in communication methods when communicating about the ending of anticancer treatment, and to identify factors contributing to the levels of emotional distress and the necessity for improvement. METHODS: A multi-center questionnaire survey was conducted on 630 bereaved family members of cancer patents who received specialized palliative care in Japan. A total of 318 responses were analyzed (effective response rate, 62%). RESULTS: Thirty-nine percent of the bereaved family members reported that they were 'very distressed' in receiving information about the ending of anticancer treatment, and 19% reported 'considerable' or 'much' improvement was necessary in the communication methods. High-level emotional distress was significantly associated with younger patient age, female family gender, the experience of the physician stating she/he could do nothing for the patient, the physician's unwillingness to explore their feelings, and prognostic disclosure of definite survival periods without probabilities or ranges. High levels of perceived necessity for improvement in the communication methods were significantly associated with the experience of the physician stating she/he could do nothing for the patient, physicians not explaining treatment goals in specific terms, physicians not pacing the explanation with the state of family preparation, physicians not being knowledgeable about the most advanced treatments, and the atmosphere not being relaxing enough to ask questions. CONCLUSIONS: In receiving the information about ending anticancer treatment, a considerable number of families experienced high levels of emotional distress and felt a need for improvement of the communication methods. The strategies to alleviate family distress could include: (i) assuring that physicians will do their best to achieve specific goals, without saying that they can do nothing for the patient; (ii) providing information, including estimated prognosis, in careful consideration of families' preparation and the uncertainty for each patient; (iii) exploring families' emotions and providing emotional support; (iv) acquiring knowledge about advanced treatments; and (v) making the atmosphere relaxing enough to allow families to ask questions.

Dissociation and decay of ultracold sodium molecules.

The dissociation of ultracold molecules was studied by ramping an external magnetic field through a Feshbach resonance. The observed dissociation energies directly yielded the strength of the atom-molecule coupling. They showed nonlinear dependence on the ramp speed. This was explained by a Wigner threshold law which predicts that the decay rate of the molecules above threshold increases with the density of states. In addition, inelastic molecule-molecule and molecule-atom collisions were characterized.

Formation of quantum-degenerate sodium molecules.

Ultracold sodium molecules were produced from an atomic Bose-Einstein condensate by ramping an applied magnetic field across a Feshbach resonance. More than 10(5) molecules were generated with a conversion efficiency of approximately 4%. Using laser light resonant with an atomic transition, the remaining atoms could be selectively removed, preventing fast collisional relaxation of the molecules. Time-of-flight analysis of the pure molecular sample yielded an instantaneous phase-space density greater than 20.

[Molecular and cellular biological analysis on cancer cachexia syndrome].

About half of patients with cancer will suffer from wasting syndrome, called cancer cachexia, which shows abnormality of homeostasis, nutrition, endocrine function, metabolism, immunity et al. This syndrome is characterized with anorexia and weight loss caused by degradation of skeletal muscle and adipose tissue. Progressive weight loss is responsible not only for a poor quality of life and poor response to anti-cancer drug, but also shorter survival time comparing patient without weight loss. Various factors have been found as mediators of this syndrome base on the development of immunology, biochemistry and molecular and cellular biology. These include several cytokines, proteolysis-inducing factor (PIF), lipid-mobilizing factor (LMF), apoptosis-inducing factor and another factors. Recentry, molecular biological analysis makes clear more detail mechanisms of cancer cachexia syndrome, for example, ubiqutin/proteasome pathway, activation of nuclear transcriptional factors and others. These progresses will contribute not only to establish new treatment but also to carry out "order-made palliative oncology" using DNA-chip and/or Protein-chip in near future.

Isolation and cultivation of porcine hepatocytes for extracorporeal artificial liver support system.

OBJECTIVE: To develop procedures for the successful harvesting of large quantities of viable and functional pig liver cells from abattoir organs. METHODS: The procedure included partial liver lobe retrograde perfusion and mechanical/enzymatic digestion of the liver tissue, followed by separation of the hepatocytes, based on size and density, from contaminating cell types. RESULTS: Digestion of the partial liver lobe resulted in an average yield of 1.39 x 10(9) cells (9.9 x 10(8) cells/g liver) with an average viability of 92.5%. The yield and viability of cells were improved by dispase/collagenase resultant digestion. The emergence of blebby cells was blocked by supplying oxygen to the cell isolation buffers. Isolated hepatocytes seeded onto polystyrene surfaces remained viable and functional at a level comparable to that of rat hepatocytes, although their function decreased over time. CONCLUSIONS: Adult pig hepatocytes can be harvested with high yields and retain viability and differentiated function using this method. Abattoir pig livers can be an excellent source of hepatocytes for use as the biological component of artificial liver assist devices.

Aldol reaction of enol esters catalyzed by cationic species paired with tetrakis(pentafluorophenyl)borate.

The crossed aldol reaction of enol esters, which are weak carbon nucleophiles, with aldehydes was effectively carried out under mild conditions by using a catalytic amount of several cationic species paired with tetrakis(pentafluorophenyl)borate.

Epirubicin-containing high-dose chemotherapy followed by autologous hematopoietic progenitor cell transfusion for patients with chemotherapy-sensitive metastatic breast cancer: results of 5-year follow-up.

PURPOSE: Conventional chemotherapy for metastatic breast cancer results in very few long-term survivors. With a view to overcoming this problem, we hypothesized that a higher rate of complete response (CR) would lead to more long-term survivors. Therefore, we conducted a phase II study of epirubicin-containing high-dose chemotherapy (HDC) followed by autologous hematopoietic progenitor cell transfusion in patients who were sensitive to induction chemotherapy. METHODS: The induction chemotherapy consisted of doxorubicin 60 mg/m2, cyclophosphamide 750 mg/m2 and fluorouracil 750 mg/m2 on day 1. Supported by G-CSF, this chemotherapy was repeated for at least three cycles at intervals of 2 weeks until the achievement of > 50% tumor regression. The HDC comprised epirubicin 120 mg/m2 on day 1, cyclophosphamide 60 mg/kg on days 1 to 3 and thiotepa 6 mg/kg on days 1 to 3, followed by autologous bone marrow transplantation and peripheral blood stem cell transfusion. RESULTS: Of 25 patients who achieved a partial response to the induction chemotherapy, 17 were treated with the HDC. Of the 15 patients evaluable for response, 10 achieved a CR (67%), giving an overall CR rate of 43% (10/25). The disease-free survival rate at 5 years was 27%. The median duration of overall survival was 21 months and the overall survival rate at 5 years was 31%. However, the survival curves were not significantly different from those of the historical controls who achieved a CR or PR to conventional chemotherapy. There were three early deaths, one as a consequence of disease progression and two treatment-related (sepsis and heart failure). Diarrhea (grade 3, 76%) and stomatitis (grade 3-4, 29%) were the dose-limiting toxicities. CONCLUSIONS: The present study suggests that epirubicin-containing HDC is able to induce a high rate of CR, but its benefit in terms of survival is still unclear. To determine whether HDC can achieve a cure in some patients, further studies in a larger number of patients, with a longer follow-up, are necessary.

[Cancer palliative medicine turning point in palliative oncology].

Hospice palliative care programs are rapidly growing in Japan. Although human science has attached importance comparing with natural science in this field, the latter approaches are recently developed to manage symptoms in terminal patients with advanced cancer. These scientific approaches include basic and clinical studies such as physiology, pharmacology, immunology, biochemistry, molecular biology, medical oncology, psycho-oncology and clinical ethics. These multidisciplinary approaches can clarify not only the mechanisms and relationship between cancer pain, cancer anorexia-cachexia syndrome and neuro-endocrine-immune systems with or without the abnormalities of body fluid, electrocyte balance, glucose-protein-lipid metabolisms but also clinical ethics and decision-making in terminal patients with advanced cancers. Based on these analyses, the strategies to modulate "homeostasis" for improving quality of life and even prolongation of life span could be developed in the near future. Our goal is to establish science-based medical practice for management of symptoms and improving the quality of life through ethical and scientific clinical trials. Hospice-palliative care in cancer would be expected to confirm what the academic area has termed "cancer palliative medicine" or "palliative oncology".

[Relationship between the presence of side-holes in bone marrow aspiration needle and the number of harvested bone marrow mononuclear cells].

The aim of this study was to evaluate the yield of nucleated cells in bone marrow harvested by means of Downs' Islam aspiration needles with or without side-holes. Twenty marrow donors for HLA identical sibling transplants were studied. Bone marrow nucleated cells were harvested 50 ml in the right iliac bone with a Downs' Islam aspiration needle with or without side-holes and 50 ml in the left with another kind of needle by means of 5 ml aspirations in each donor. There were no significant difference between the number of nucleated cells by means of Downs' Islam aspiration needles with and without side-holes by cross-over analysis. All nucleated cell counts were 33.06 +/- 12.93 x 10(3)/microliter (mean +/- standard deviation) by means of the needle with side-holes and 32.90 +/- 15.25 x 10(3)/microliter by means of the needle without side-holes. The Downs' Islam aspiration needle without side-holes seems to be better in bone marrow harvest from normal volunteers than that with side-holes, because the former may be stronger than the latter.

Construction of AB-ring system of taxane framework by A-ring annulation strategy: synthesis of 1-hydroxy-8,11,11-trimethylbicyclo-[5.3.1]undec-7-en-9-one by way of intramolecular aldol cyclization to form the C1-C10 bond.

Construction of the AB-ring system of the taxane framework via an A-ring annulation strategy was demonstrated by base-mediated intramolecular aldol reaction of (Z)-2,2-dimethyl-3-(1-methyl-2-oxopropylidene)cyclooctanone, affording the title compound, 1-hydroxy-8,11,11-trimethylbicyclo[5.3.1]undec-7-en-9-one. A cyclization precursor, the tetra-substituted (Z)-alkene, was prepared from the corresponding cyclooctanone derivative, 3-[(alpha,alpha- dimethylbenzyl)dimethylsiloxy]-2,2-dimethylcyclooctanone via a bicyclic alpha,beta-unsaturated lactone intermediate.

Preparation of useful synthetic intermediates of Taxol analogs, cyclooctenone derivatives.

Stereoselective syntheses of omega-(alpha-bromoketo) octanals and nonanal with oxygenated functions and formation of the corresponding eight-membered carbocyclic aldols by subsequent samarium(II)-mediated cyclization are demonstrated. Cyclooctenones deoxygenated at the C2 or C10 position in the taxane framework are prepared by dehydration of the above aldols.

High-dose chemotherapy with peripheral blood stem-cell transplantation for hormone-refractory advanced carcinoma of the prostate: experience of two cases.

Two patients with hormone-refractory advanced prostate cancer were treated with high-dose chemotherapy and peripheral blood stem-cell transplantation. A satisfactory number of stem cells were collected by appropriately timed leukapheresis in these patients. The stem-cell samples collected from the first patient were positive for prostate-specific antigen messenger ribonucleic acid expression; such expression was not detected in the samples from the second patient. The first patient has remained in complete remission as of December 1995. The second patient died of the disease.

[Autologous hematopoietic stem cell transplantation for the treatment of breast cancer].

To obtain higher anti-tumor efficacy for breast cancer (BC), high-dose chemotherapy (HDC) with autologous bone marrow transplantation (ABMT) and peripheral blood stem cell transplantation (PBSCT) is believed to be one of most effective strategies. PBSCT shows earlier hematological recovery comparing with ABMT, therefore HDC could be performed more safety to introduce PBSCT in the treatment of BC. Several investigators have reported that higher complete response (CR) rate and continuously CR rate were obtained to employ HDC in the earlier course of treatment for patient with advanced or recurrent BC responding to standard-dose chemotherapy. The efficacy of HDC has been also observed in adjuvant setting for patient with high-risk (> or = 10 axillary lymph nodes) after mastectomy. Phase III studies will clarify the efficacy of HDC with ABMT, PBSCT for the treatment of BC in near future.

Peripheral blood stem cell mobilization with chemotherapy and granulocyte-colony stimulating factor in patients with hematological malignancies.

Peripheral blood stem cell (PBSC) transplantation (PBSCT) following high-dose chemotherapy is considered to be an effective and curative strategy for patients with certain malignancies. Optimal conditions for collection of PBSC and successful PBSCT, however, are still controversial. We performed 57 leukaphereses after 19 courses of chemotherapy for mobilization of PBSC (semi-high-dose VP-16 alone; 500 mg/m2/day for 3 or 4 days, 13 courses, or conventional chemotherapy; six courses) combined with subsequent G-CSF administration in 13 patients with malignancies (six with lymphoma, five with leukemia, and two with germ cell tumors). Total numbers of the CD34+ cells and CFU-GM obtained by multiple leukaphereses after one course of mobilization therapy were 0.63-168.74 x 10(6)/kg (mean 33.94) and 0.15-56.0 x 10(5)/kg (mean 8.22), respectively. We demonstrated that many cellular components of peripheral blood (PB) on the day of PBSC harvest, especially CD34+ cell, total leukocyte, myelocyte and monocyte counts, were correlated with the numbers of CFU-GM obtained in each leukapheresis. A daily increase of leukocyte counts was another useful indicator for the day of PBSC harvest. We also found that the time when total leukocyte counts in PB recovered to more than 5000/microliters or when CD34+ cells within PB mononuclear cells exceeded 1% was optimal for PBSC harvest. Our results confirmed that the semi-high-dose regimen with VP-16 combined with G-CSF is a safe method which has both antitumor effects and mobilization ability of PBSC in patients with hematological malignancies. PBSCT following various high-dose chemotherapy regimens with or without total body irradiation was also performed in 11 of the 13 patients, and rapid hematologic recovery was observed in all of the patients.

[Phase I study of paclitaxel].

Paclitaxel, a novel antimicrotubule agent that enhances tubulin polymerization and microtubule stability, was administered as a 24-hour infusion in a phase I study. Twelve patients received 32 courses at 50, 100, 150, and 200 mg/m2. A premedication regimen of dexamethasone, diphenhydramine, and ranitidine was used to prevent the acute hypersensitivity reactions (HSRs). The dose-limiting factor was leukopenia (granulocytopenia) associated with Grade 4 infection. The maximum tolerated dose was 200 mg/m2. Other non-hematological effects included peripheral neuropathy, myalgia, alopecia, and elevations of transaminase and alkaline phosphatase. Severe HSRs were not observed. The paclitaxel plasma concentration declined with a half-life of 10.0 to 24.9 hours. Excretion into urine within 72 hours was in the range of 7.28 to 11.34% of paclitaxel dosage. Two patients with breast cancer at the 200 mg/m2 dose level had partial responses. The recommended dose of paclitaxel for phase II study, when administered as a 24-hour infusion, is considered to be 150 mg/m2 every 3 weeks.

[Treatment strategy to obtain cure for recurrent advanced breast cancer].

The three-year survival rate of a total of 186 patients with recurrent advanced breast cancer was 86% for complete responders, 27% for partial responders, and 29% for patients remaining in stable diseases, respectively, at our two institutions. Thus, the results indicated that a complete response is the first step for long-term survival. High-dose chemotherapy with autologous stem cell support was administered after 4 cycles of induction chemotherapy. The results showed 12 complete response (60%) out of 20 patients, and 5 cases survived with no evidences of disease for 5-31 months. Both taxol and taxotere achieved response rates exceeding 50% in phase II trials on advanced breast cancer and therefore were expected to have a role in combination regimens with other drugs.

Isolation of human CD34+ peripheral blood stem cells using an immunomagnetic positive selection system: prior monocyte depletion using a nylon-wool column.

An immunomagnetic separation system has been used to collect CD34+ cells in mobilized blood after treatment with a nylon-wool column. Cell purities were increased from 2.6% preseparation to 94.6% postseparation, with a mean yield 45.2% (n = 4). Forty percent of CD34+ cells separated by the immunomagnetic procedure formed colonies in the presence of hematopoietic growth factors in a limiting dilution assay. Eleven percent of these clones proliferated to over 10(5) cells and contained megakaryocytes.

[Phase I and pharmacokinetic study of SM-5887 by 5-day schedule].

Pharmacokinetics of SM-5887, a new totally synthetic anthracycline derivative, was studied in a phase I setting by 5-day schedule. The maximum tolerated dose was 25 mg/m2/d (total dose: 125 mg/m2/body) and the dose-limiting toxicity was myelosuppression which was consistent with the results of the phase I study by a single dose. In terms of subjective side effects, decreased nausea/vomiting and increased stomatitis were observed. In pharmacokinetic study, AUC of active form of SM-5887 increased on day 5 compared to that day 1. This result suggested that 5-day schedule of SM-5887 produced an accumulation of the active form. Five-day treatment schedule of SM-5887 seems to be more tolerable and further clinical study was recommended.