Characterization of the anticancer properties of monoglycosidic cardenolides isolated from Nerium oleander and Streptocaulon tomentosum

Aim of the study

For identification of the active constituents we investigated the anticancer activity of cardenolides from Streptocaulon tomentosum Wight & Arn. (Asclepiadaceae) and from Nerium oleander L. (Apocynaceae) which are both used against cancer in the traditional medicine in their region of origin.

Material, methods and results

The antiproliferative activity of cardenolides isolated from roots of Streptocaulon tomentosum (IC₅₀ < 1-15.3 μM after 2 days in MCF7) and of cardenolide containing fractions from the cold aqueous extract of Nerium oleander leaves (“Breastin”, mean IC₅₀ 0.85 μg/ml in a panel of 36 human tumor cell lines), their influence on the cellular viability and on the cell cycle (block at the G2/M-phase or at the S-phase in tumor cells, respectively) were determined using different cell lines. The murine cell line L929 and normal non-tumor cells were not affected. Bioactivity guided fractionation of Breastin resulted in the isolation of the monoglycosidic cardenolides oleandrine, oleandrigeninsarmentoside, neritaloside, odoroside H, and odoroside A (IC₅₀-values between 0.010 and 0.071 μg/ml).

Conclusions

The observed anticancer activities of extracts and isolated cardenolides are in agreement with the ethnomedicinal use of Streptocaulon tomentosum and Nerium oleander. The most active anticancer compounds from both species are monoglycosidic cardenolides possessing the 3β,14β-dihydroxy-5β-card-20(22)-enolide structure with or without an acetoxy group at C-16. The results indicate that the cytotoxic effects are induced by the inhibition of the plasma membrane bound Na⁺/K⁺-ATPase.     

Podoplanin expression predicts prognosis in patients with oral squamous cell carcinoma treated with neoadjuvant radiochemotherapy

Despite new therapeutic approaches patients with advanced oral squamous cell carcinoma still have a dismal prognosis. The main factor contributing to this problem is locoregional failure due to a lack of response to treatment. Several trials have proven the effect of neoadjuvant radiochemotherapy followed by radical surgery in comparison to primary surgery followed by adjuvant radiochemotherapy. No reliable parameters have been identified so far to predict response to radiochemotherapy. The aim of our study was to assess whether podoplanin expression in pretreatment biopsies could serve as a biomarker to predict the host response to neoadjuvant radiochemotherapy.In this retrospective study, podoplanin expression was examined in a set of 63 patients with oral squamous cell carcinoma by immunohistochemistry. We analyzed associations between the level of podoplanin expression and various clinicopathologic parameters, including response to radiochemotherapy, clinical and histological N-status. Furthermore we evaluated the effects of these parameters on overall survival and on locoregional control in univariate and multivariate analysis.The χ²-test revealed that high expression of podoplanin in pretreatment biopsy material was associated with non-regression of the tumor (p = 0.013) and poor overall survival (p < 0.001). Five-year survival rates of 92.9% for patients with weak expression and 15.0% for high expression were revealed. Podoplanin expression was also significantly associated with ypN status (p = 0.004) and ypUICC status (p < 0.001).We concluded that podoplanin might serve as a factor to predict treatment response in oral squamous cell carcinoma treated with neoadjuvant platin-based radiochemotherapy as well as a prognostic factor for overall survival and locoregional control.     

The antiapoptotic gene survivin is highly expressed in human chondrosarcoma and promotes drug resistance in chondrosarcoma cells <Emphasis Type="Italic">in vitro</Emphasis>

Background  

Chondrosarcoma is virtually resistant to chemotherapy and radiation therapy. Survivin, the smallest member of the inhibitor of apoptosis protein family, is a critical factor for tumor progression and resistance to conventional therapeutic approaches in a wide range of malignancies. However, the role of survivin in chondrosarcoma has not been well studied. We examined the importance of survivin gene expression in chondrosarcoma and analysed its influences on proliferation, apoptosis and resistance to chemotherapy in vitro.     

The important role of radiation therapy in early-stage diffuse large B-cell lymphoma: time to review the evidence once again

Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin's lymphoma in the USA, and approximately one-third of patients present with early stage, localized disease. While significant controversy still exists regarding the appropriate management of these patients, the overwhelming evidence from a wide range of studies over the last 40 years points to the superior efficacy of combined-modality therapy for this disease. The current standard of care for the vast majority of early-stage DLBCL cases now involves a combination of chemotherapy, immunotherapy and consolidation radiotherapy. Using this multimodality approach, very high rates of local control can be achieved, which will translate into significant survival benefits for patients with localized disease. The use of intensive immunochemotherapy without radiation therapy requires formal testing and validation in a randomized clinical trial before it can be used as an alternative treatment regimen for early-stage DLBCL. In this article, we discuss the results of the key randomized trials, critical retrospective studies and recent clinical trials, which collectively address the important role of radiotherapy in the treatment of early-stage DLBCL.     

Aggressive fibromatosis of the head and neck: a new classification based on a literature review over 40 years (1968–2008)

Background

Fibromatosis is an aggressive fibrous tumor of unknown etiology that is, in some cases, lethal. Until now, there has been no particular classification for the head and neck. Therefore, the aim of the present study was to review the current literature in order to propose a new classification for future studies.

Methods

An evidence-based literature review was conducted from the last 40 years regarding aggressive fibromatosis in the head and neck. Studies that summarized patients’ data without including individual data were excluded.

Results

Between 1968 and 2008, 179 cases with aggressive fibromatosis of the head and neck were published. The male to female ratio was 91 to 82 with a mean age of 16.87 years, and 57.32% of the described cases that involved the head and neck were found in patients under 11 years. The most common localization was the mandible, followed by the neck. All together, 143 patients were followed up, and in 43 (30.07%), a recurrence was seen.

Conclusion

No clear prognostic factors for recurrence (age, sex, or localization) were observed. A new classification with regard to hormone receptors and bone involvement could improve the understanding of risk factors and thereby assist in future studies.     

Expression of cyclooxygenase-2 (COX-2) in an advanced metastasized hypopharyngeal carcinoma and cultured tumor cells

Purpose

The inducible enzyme cyclooxygenase-2 (COX-2) catalyzes PGE₂ production and plays an important role in the progression of many solid cancers. However, the role of COX-2 expression in cervical lymph node metastases of head and neck cancer has not been clarified yet.

Patient and methods

We comment on a male patient aged 53 who was admitted to an ENT-department with acute bleeding from an advanced hypopharyngeal carcinoma and a frontotemporal mass. Prior to palliative intended radiotherapy, the metastasis was resected. During the procedure, a small amount of tumor tissue was harvested for primary tumor cell culture.

Results

COX-2 overexpression was demonstrated in the primary tumor tissue, the metastasis, in the cultured tumor cells by standard immunohistochemistry, as well as cytochemistry.

Conclusions

A simultaneous expression of COX-2 in head and neck carcinoma was presented for the first time. Besides the prognostic impact in oral carcinogenesis, this COX-2 role of biomarker for aggressive head and neck squamous cell carcinomas should be further evaluated. Additionally, treatment of hypopharyngeal carcinomas with selective COX-2 inhibitors could be beneficial when administered in combination with radiochemotherapy.