Capecitabine and mitomycin C is an effective combination for anthracycline- and taxane-resistant metastatic breast cancer

Capecitabine is converted to 5-fluorouracil by thymidine phosphorylase, and mitomycin C is capable of upregulating the expression of thymidine phosphorylase suggesting a synergistic effect. Fifty-three patients (median age 62 years) with anthracycline- and taxane-resistant, metastatic breast cancer received mitomycin C 6 mg/m(2) on day 1, and capecitabine (Xeloda) 2,000 mg/m(2)/day from day 1 to day 14 with cycles repeated every 4 weeks. Overall, 77.4% had visceral metastases and 33 were pretreated with >/=3 chemotherapy lines. A median of 6 cycles were given (range 1-19) with a complete response observed in 2 patients (3.9%), partial response in 17 (33.3%) and stable disease in 19 (37.2%). Overall response rate was 37.2% (95% CI, 24.0-50.5%), with a median duration of 10.4 months. Median time to progression was 8.1 months and median survival was 17.4 months (1- and 2-year survival rates of 60 and 28%, respectively). Toxicity was mild. The most frequent grade 3/4 events were neutropenia (5.7% of patients), diarrhea (3.8%), and deep venous thrombosis (3.8%). Capecitabine plus mitomycin C may represent an effective and manageable treatment option for advanced breast cancer patients resistant to anthracyclines and taxanes. This approach provides an alternative for pretreated patients with advanced breast cancer.     

Tubular adenoma of the breast in an 84-year-old woman: report of a case simulating breast cancer

Tubular adenomas of the breast are rare and they mainly occur in young women. They must be differentiated from other benign lesions and from malignant breast cancer. Preoperative diagnosis is difficult because both radiologic and cytohistologic examinations performed before surgery are often not diagnostic; therefore, in most cases, surgical excision is the only way to reach a precise diagnosis and a definitive treatment. This article describes a case of an 84-year-old woman suffering from tubular adenoma of the breast. The authors underline the difficulty in preoperative differentiation between benign and malignant breast lesions.     

Preliminary data on Pemphigus vulgaris treatment by a proteomics-defined peptide: a case report

Background

A functional blood supply is essential for tumor growth and proliferation. However, the mechanism of blood vessel recruitment to the tumor is still poorly understood. Ideally, a thorough molecular assessment of blood vessel cells would be critical in our comprehension of this process. Yet, to date, there is little known about the molecular makeup of the endothelial cells of tumor-associated blood vessels, due in part to the difficulty of isolating a pure population of endothelial cells from the heterogeneous tissue environment.

Methods

Here we describe the use of a recently developed technique, Expression Microdissection, to isolate endothelial cells from the tumor microenvironment. The methylation status of the dissected samples was evaluated for GSTP1 and RARβ2 promoters via the QMS-PCR method.

Results

Comparing GSTP1 and RARβ2 promoter methylation data, we show that 100% and 88% methylation is detected, respectively, in the tumor areas, both in epithelium and endothelium. Little to no methylation is observed in non-tumor tissue areas.

Conclusion

We applied an accurate microdissection technique to isolate endothelial cells from tissues, enabling DNA analysis such as promoter methylation status. The observations suggest that epigenetic alterations may play a role in determining the phenotype of tumor-associated vasculature.     

Praxic and executive components in tool use learning: the role of imitation

Recent research in comparative psychology suggests that similarities between the behaviour of two individuals may not be the consequence of imitation only, but also of nonimitative social-learning processes. In the present study we aimed to investigate whether these alternative learning processes can take place in human adults, specifically in patients whose ability to imitate has been reduced by brain damage. Left (LBD) and right (RBD) brain-damaged patients were asked to perform four tool use tasks in three experimental conditions: exposure to the apparatus (N); demonstration of the correct solution (C); and demonstration of a failed attempt followed by the correct solution to the problem (I + C). Results suggest that the left hemisphere is indeed critical for action and that selective neuropsychological deficits can affect action imitation and selection of goal-directed movements, independently from each other. Findings also indicate that when the ability to imitate actions is lowered emulation may become available.     

'Role of bone marrow stromal cells in the growth of human multiple myeloma.

We have verified the hypothesis that multiple myeloma (MM) may be disseminated by circulating clonogenic cells that selectively home to the bone marrow (BM) to receive the signal(s) leading to proliferation, terminal differentiation, and production of the osteoclast activating factors. Long-term cultures of stromal cells have been developed from the BM of nine patients with MM. These cells were mostly fibroblast-like elements, interspersed with a proportion of scattered macrophages and rare osteoclasts. BM stromal cells were CD54+, produced high levels of interleukin-6 (IL-6) and measurable amounts of IL-1 beta, and were used as feeder layers for autologous peripheral blood mononuclear cells (PBMC). After 3 weeks of cocultures, monoclonal B lymphocytes and plasma cells, derived from PBMC, developed and the number of osteoclasts significantly increased. Both populations grew tightly adherent to the stromal cell layer and their expansion was matched by a sharp increase of IL-6 and by the appearance of IL-3 in the culture supernatant. These data attribute to BM stromal cells a critical role in supporting the growth of B lymphocytes, plasma cells, and osteoclasts and the in vivo dissemination of MM.     

The osteoclasts of hen medullary bone under hypocalcaemic conditions

Summary Osteoclasts of medullary bone after several days of hypocalcaemic diet are substituted on the trabecular surface by active osteoblasts. The fate and the ultrastructure of the osteoclasts withdrawn from medullary bone surfaces in the course of a low calcium diet has been studied in serial semithin and ultrathin sections. The cytoplasmic surface of osteoclasts located in marrow compartments presents blebs and protrusions and the whole cell is often irregularly branched in several directions. A large amount of granular endoplasmic reticulum is accumulated at the cell periphery; often the cisternae are distended to form vesicles with an inner core of dense material. Osteoclasts seem to divide into mono or polynucleated smaller units.