Quantitative assessment of contaminating tumor cells in autologous peripheral blood stem cells of B-cell non-Hodgkin lymphomas using immunoglobulin heavy chain gene allele-specific oligonucleotide real-time quantitative-polymerase chain reaction

A real-time quantitative-polymerase chain reaction (RQ-PCR) targeting the immunoglobulin heavy chain (IgH) gene has been used for the quantification of minimal residual disease (MRD) in B-cell hematological malignancies. In non-Hodgkin lymphoma (NHL), experimental costs are increased, as a large number of primer-probe sets are required because of diversity, due to somatic and ongoing mutations of the IgH gene. We developed an allele-specific oligonucleotide (ASO) combined with a germline consensus probe-based RQ-PCR assay and examined MRD in peripheral blood stem cells (PBSC). The IgH consensus probes were adapted in seven (50%) of 14 amplifiable cases. Patients with heavily contaminating tumor cells in PBSC relapsed after PBSC transplantation. Our strategy will contribute to the development of a cost-efficient, precisely quantitative and systemic detection assay for MRD in NHL.     

Caffeine diminishes cytotoxic effects of paclitaxel on a human lung adenocarcinoma cell line

This study was performed to investigate how caffeine modifies the cytotoxic effects of paclitaxel on a human lung carcinoma cell line. Caffeine doses up to 5mM had less effect on clonogenic survival. The cell killing effect, due to paclitaxel, increased in a dose-dependent manner up to 50 nM. For combined treatment with caffeine and paclitaxel, added caffeine reduced the cytotoxic effect of paclitaxel not only in dose-response but also in time-response curves. Caffeine combined with paclitaxel clearly suppressed cell proliferation in a dose-dependent manner. In the cell cycle analysis, caffeine alone caused early G1 accumulation, whereas paclitaxel alone caused an early increase in G2-M and a decrease in G1. As for the effect of caffeine on paclitaxel, caffeine suppressed the effect of paclitaxel on cell cycle distribution, where a dose-dependent early increase in G2-M and a decrease in G1 were not clear. We suggest that cell cycle modifying agents, such as caffeine, potentially diminish the cytotoxic activity of paclitaxel, and one should be careful when combining such agents.     

Process of care and preliminary outcome in limited-stage small-cell lung cancer: results of the 1995-1997 patterns of care study in Japan

PURPOSE: To evaluate the practice process using the national average (NA); to compare differences in the process of care by age group; and to provide a preliminary outcome data for limited-stage small-cell lung cancer in Japan. METHODS AND MATERIALS: The Patterns of Care Study conducted a nationwide survey of the care process for Stage I-III small-cell lung cancer in Japan. Patients were divided into three age groups: <65 years (younger group, n = 73); between 65 and 74 years (intermediate group, n = 81); and >or=75 years (elderly group, n = 20). RESULTS: The NA for the total dose was 49.0 Gy, and for use of photon energy >or=6 MV, chemotherapy, and prophylactic cranial irradiation was 77.3%, 93.2%, and 1.69%, respectively. Age stratification had no impact on the variables of radiotherapy (RT) such as total dose and field size. Only 37% of patients received chemotherapy and thoracic RT concurrently. The proportion of patients who received chemotherapy and RT concurrently was 44%, 27%, and 25% of the younger, intermediate, and elderly groups, respectively (p = 0.029). Etoposide and cisplatin were less frequently used in the elderly group (>or=75 years old). Overall survival at 3 years for the entire group was 26%. The 3-year survival rate was 30% in the younger group, 28% in the intermediate group, and 9% in the elderly group. Variables found to have a significant impact on survival by multivariate analysis were the use of chemotherapy (p = 0.030), age (p = 0.032), and T stage (p = 0.042). CONCLUSION: Calculated NAs showed that the results of clinical study had favorably penetrated into the practice process in Japan. The results demonstrated that patient age significantly influenced the process of chemotherapy such as the use of etoposide and cisplatin for limited-stage small-cell lung cancer in Japan. More concurrent chemotherapy and thoracic RT and the application of prophylactic cranial irradiation for complete responders need to be investigated in the future.     

Effect of nedaplatin, 5-FU,and leucovorin combined with radiation therapy in unresectable esophageal carcinoma

A 51-year-old male was assessed as having esophageal squamous cell carcinoma with trachea invasion and cervical lymph node metastasis. After one course of chemotherapy using cisplatin (CDDP), 5-fluorouracil (5-FU) and Leucovorin (LV), the patient had progressive disease (PD) of the primary lesion and metastatic lymph nodes, and a side effect of severe nausea. One course of nedaplatin, 5-FU and LV combined with radiation was performed alternatively. The effect was evaluated as a partial response (PR) of the primary lesion and metastatic lymph nodes. There were no adverse side effects such as nausea or renal dysfunction except for pancytopenia of grade 2. Increased serum levels of vascular endothelial growth factor (s-VEGF) decreased after the chemoradiotherapy and increased again during continued radiotherapy alone. More information is needed as to whether changes in s-VEGF relate to the clinical effects of the treatment.     

Clinical study of weekly paclitaxel administration for metastatic breast cancer based on time to progression (TTP) and survival

We studied 13 women aged 29-62 years for response to weekly administration of paclitaxel for metastatic breast cancer. Paclitaxel was administered by 1-hour intravenous infusion at a dose of 60-80 mg/m2 once a week. Administration was continued for 3 weeks with a 1-week rest for at least 3 cycles. This was first-line treatment in 1 patient, second-line treatment in 7, and third-line treatment in 5. The overall response rate was 68% among 13 partial responders and there were no complete responders. By recurrence site, the response rate was 71% in the liver, 75% in the lung, 18% in bone, and 67% at local sites. Pain was ameliorated in 4 of 8 patients and local recurrence of tumors decreased in 6 of 8 cases. Tumor markers decreased in 6 of 12 cases. Time to progression reached beyond 6 months in 6 of 13 cases, and was limited to within only 3 months in 6 cases. In terms of survival, 4 of 13 patients who were treated by paclitaxel as a 3rd line treatment for liver or lung metastasis died within 3 months after administration. Weekly administration of paclitaxel appears to be effective against metastatic breast cancer. However, the selection of cases based on the timing of administration is considered to be important to prolong the time to progression and improve survival.     

A development of the network for functional trainings in daycare services in a large district

After the Long-Term Care Insurance (LTCI) regulation has been enacted, all the daycare agencies/institutions must provide functional trainings to their clients as one of the standard services. However, the regulation is limited only to their personnel arrangement rather than the service content, which is left to each agency/institution. We feel that functional trainings as a daycare service need more attention so that we can bridge the content gaps between agencies/institutions. To solve this problem, we planned to send training professionals to these daycare providers in the surrounding areas. At the same time, we have been holding training courses for daycare stuff and each trainer, which contributed to fill the knowledge and skill gaps between these trainers'. The purpose of this paper is to report our study with some suggestions about the ideal functional trainings in the future daycare services.     

Antitumor effect by interleukin-11 receptor alpha-locus chemokine/CCL27, introduced into tumor cells through a recombinant adenovirus vector

In this study, we examined antitumor activity of a mouse CC chemokine ILC/CCL27 and a mouse CX(3)C chemokine fractalkine/CX(3)CL1 in vivo. We generated recombinant adenovirus vectors with a fiber mutation, encoding mILC (Ad-RGD-mILC) and mFKN (Ad-RGD-mFKN). We confirmed tumor cells infected with Ad-RGD-mILC and Ad-RGD-mFKN to express and release these chemokines. Tumor rejection experiments in vivo were carried out by inoculating OV-HM cells infected with Ad-RGD-mILC or Ad-RGD-mFKN into immunocompetent mice. mILC significantly suppressed the tumor growth, whereas no such significant effect was observed by mFKN. The antitumor activity induced by mILC was T cell dependent, involving both CD4(+) and CD8(+) T cells. Immunohistochemical analysis revealed accumulation of both CD3(+) lymphocytes and NK cells in the tumor tissue transduced with mILC and mFKN. However, there was a significant difference in the distribution of infiltrating cells. Furthermore, mFKN appeared to have an angiogenic activity, which might have masked its tumor suppressive activity. Collectively, ILC/CCL27 may be a good candidate molecule for cancer gene therapy.