Advanced chemoresistant breast cancer responding to multidisciplinary treatment with hyperthermia, radiotherapy, and intraarterial infusion.

We employed multidisciplinary therapy, consisting of hyperthermia, radiotherapy, and intraarterial infusion, for a patient with progressive advanced breast cancer that was resistant to epirubicin hydrochloride and cyclophosphamide (EC) therapy as well as being resistant to docetaxel hydrate, and obtained a good therapeutic response. Because estrogen and progesterone receptors were both negative and HER2 was 3(+), administration of trastuzumab was started, and this patient has shown no signs of recurrence at 33 months after our treatment. The results suggested that our multidisciplinary therapy can be an effective method for the treatment of progressive breast cancer showing resistance to major chemotherapy agents such as anthracyclines and taxanes.

[The repetitive immune cell transfer therapy combining non-myelosuppressive chemotherapy for patients with advanced and refractory cancer].

Autologous tumor cells stimulated with T lymphocytes (AuTL) were generated ex vivo from peripheral blood lymphocytes over a two-week co-culturing process with autologous tumor cells. These AuTLs were capable of lysing established tumor cell lines and may have a potential for efficacy as an adoptive immunotherapy (IT) in advanced and metastatic refractory cancer patients (pts). We investigated the feasibility of a combination of AuTL transfer and chemotherapy (ChT) based on the conventional conditioning regimen in order to take advantage by both the anticancer effects and reconstruction of antitumor immunity. Nineteen patients were enrolled in a pilot clinical trial. The two administrations of AuTL were given prior to chemotherapy (ChT) for one treatment cycle. The treatment was repeated at least for three cycles over a one-week interval. The conventional ChT regimen was based on the standard dosage. The pts consisted of 3 of gastric cancer, colon cancer, lung adenocarcinoma, respectively, 6 of esophageal cancer, and 2 of breast and pancreas carcinoma, respectively. AuTLs were administered 1x/2 weeks using direct injection or intraarterial infusion. The median duration of the treatment was over 11.5 months, and the median survival time was 14.8 months. Adverse events related to both the ChT and AuTL transfers at all dosages were minimal. Four of the 13 pts achieved major tumor responses (2 CR: complete regression and 2 PR: partial regression) in this study. Three pts showed progressive disease, and 6 pts had stable disease for over 90 days. PBMC were evaluated for cytokine production prior to the treatment and after 3 treatments. Two and one of 4 CR/PR pts had increased IFN-gamma and TNF-alpha production with no TGF-beta1 responses by their PBMC after 3 treatments, respectively. Two out of 6 pts who experienced stable disease after the treatment had high IFN-gamma and TNF-alpha responses and no TGF-beta1 or IL-4 response. TGF-beta1 and IL-4 secretion increased in parallel in 3 out of 3 pts that experienced progressive disease after the treatment. These data show that combination therapy of AuTL transfer and non-myeloablative ChT is a feasible option for patients with refractory advanced cancers without serious adverse events and without reducing Th1 cytokine responses in peripheral blood for most of the pts that responded to the treatment. According to each mechanism of IT and ChT, a more stringent evaluation of AuTL transfer combined with non-myeloablative ChT for various kinds of cancers should be performed to manage the immunodeficiency in the pts with advanced cancer and to improve the effect of antitumor AuTLs.

Axillary lymph node recurrence of papillary thyroid microcarcinoma: report of a case.

We report a case of axillary lymph node recurrence of thyroid papillary microcarcinoma (PMC) in a 51-year-old woman who had undergone thyroidectomy with lymph node dissection 5 years earlier. We performed residual thyroid resection with cervical and bilateral axillary lymph node dissection, and pathological examination revealed well-differentiated papillary carcinoma, with partial poor differentiation. Postoperative radioiodine therapy was ineffective, and the patient died of systemic dissemination of the recurrence 8 months after her second operation. The positive cell rates of proliferating cell nuclear antigen and Ki-67 were clearly higher in the recurrent lymph nodes than in the primary thyroid tumor, suggesting increased cell proliferation in the recurrent lymph nodes. Thyroid papillary carcinoma rarely recurs in the axillary lymph nodes, but its possibility must be kept in mind, especially in patients with remarkable cervical lymph node metastasis and those who undergo extensive lymph node dissection.

Prevention of carcinogenesis of mouse mammary epithelial cells RIII/MG by epigallocatechin gallate.

The chemopreventive effect of the polyphenols abundant in green tea on carcinogenesis has been attracting attention in recent years. Among tea polyphenols, epigallocatechin gallate (EGCG) has been studied as a preventive substance for carcinogenesis. We investigated the chemopreventive effect in a group treated with EGCG in vitro and in vivo using mouse mammary epithelial cells RIII/MG. In the in vitro experiment, crude catechin (catechin) containing 50% or more EGCG significantly inhibited the growth of RIII/MG cells, which were precancerous cultured cells. Many cells died, and a DNA ladder was observed. In the in vivo experiment, RIII/MG cells formed a tumor after 13 weeks in a group without catechin treatment, and the tumor formation rate in the 20th week was 40%. In a group treated with 0.1% catechin, a tumor began to grow in the 13th week, and the tumor formation rate in the 20th week was 20%. In a group treated with 1% catechin, no tumor was detected even in the 20th week. There was no significant difference in the change in body weight between the catechin treatment groups and the non-treatment group during the observation period. Tissue samples were stained by the nick-end-labeling method and apoptosis was observed in many cells. Based on the above findings, EGCG inhibited growth in the mouse viral mammary epithelial carcinogenesis model RIII/MG, and induced apoptosis, suggesting a clinical usefulness of EGCG as a chemopreventive substance.