A prospective, controlled study of the botanical compound mixture LCS101 for chemotherapy-induced hematological complications in breast cancer

Background.

This prospective, controlled study evaluated the safety, tolerability, and efficacy of the mixture of botanical compounds known as LCS101 in preventing chemotherapy-induced hematological toxicity in breast cancer patients.

Methods.

Female patients diagnosed with localized breast cancer were randomly allocated to receive treatment with either LCS101 or placebo capsules, in addition to conventional chemotherapy. The study intervention was initiated 2 weeks prior to the initiation of chemotherapy and continued until chemotherapy was completed, with participants receiving 2 g of LCS101 capsules thrice daily. Subjects were assessed for the development of hematological and nonhematological toxicities, as well as the tolerability and safety of the study intervention.

Results.

Sixty-five breast cancer patients were recruited, with 34 allocated to LCS101 and 31 allocated to placebo treatment. Patients in the treatment group developed significantly less severe (grades 2–4) anemia (p < .01) and leukopenia (p < .03) when comparing grades 0–1 with grades 2–4, with significantly less neutropenia (p < .04) when comparing grades 0–2 with grades 3–4. This effect was more significant among patients undergoing a dose-dense regimen. No statistically significant effect was found with respect to nonhematological toxicities, and side effect rates were not significantly different between the groups, with no severe or life-threatening events observed in either group.

Conclusion.

The addition of LCS101 to anthracycline- and taxane-based chemotherapy is safe and well tolerated, and may significantly prevent some chemotherapy-induced hematological toxicities in early breast cancer patients. These results should encourage further larger and more extensive clinical trials.     

A comparison of the effect of lead nitrate on rat liver chromatin, DNA and histone proteins in solution

Although lead is widely recognized as a toxic substance in the environment and directly damage DNA, no studies are available on lead interaction with chromatin and histone proteins. In this work, we have examined the effect of lead nitrate on EDTA-soluble chromatin (SE chromatin), DNA and histones in solution using absorption and fluorescence spectroscopy, thermal denaturation and gel electrophoresis techniques. The results demonstrate that lead nitrate binds with higher affinity to chromatin than to DNA and produces an insoluble complex as monitored at 400 nm. Binding of lead to DNA decreases its Tm, increases its fluorescence intensity and exhibits hypochromicity at 210 nm which reveal that both DNA bases and the backbone participate in the lead–DNA interaction. Lead also binds strongly to histone proteins in the absence of DNA. The results suggest that although lead destabilizes DNA structure, in the chromatin, the binding of lead introduces some sort of compaction and aggregation, and the histone proteins play a key role in this aspect. This chromatin condensation, upon lead exposure, in turn may decrease fidelity of DNA, and inhibits DNA and RNA synthesis, the process that introduces lead toxicity at the chromatin level.     

Normal ranges of angiogenesis regulatory proteins in human platelets

Platelets sequester angiogenesis regulatory proteins early in tumor growth, which suggests a new avenue for monitoring disease. To date, there are no clinically relevant reference ranges for markers of early angiogenesis. We introduce a new ELISA‐based method for accurate and reproducible measurement of vascular endothelial growth factor (VEGF), platelet‐derived growth factor (PDGF), platelet factor 4 (PF4), thrombospondin‐1 (TSP‐1), fibroblast growth factor, basic (bFGF), and endostatin in platelets. To facilitate clinical applicability, the platelet levels in isolated samples were determined utilizing a new actin ELISA method. Platelets from healthy donors at single and repetitive time points were used for the assessment of normal ranges of these proteins. The physiological levels in platelets were: VEGF (0.74 ± 0.37 pg/10⁶ platelets); PDGF (23 ± 6 pg/10⁶); PF4 (12 ± 5 ng/10⁶); TSP‐1 (31 ± 12 ng/10⁶); bFGF (0.44 ± 0.15 pg/10⁶); and endostatin (5.6 ± 3.0 pg/10⁶). There was an excellent correlation (R² = 0.7) between the platelet levels calculated with the actin ELISA and complete blood count. The levels of the platelets were higher than those in platelet‐poor plasma by factors of: VEGF (215‐fold); PDGF (914‐fold); PF‐4 (516‐fold); TSP‐1 (813‐fold); and bFGF (17‐fold). The endostatin levels were nearly equivalent. The biovariability of the platelet proteins in eight healthy subjects over a 5‐week period was found to be minimal. We describe accurate and direct measurements of the concentrations of VEGF, bFGF, PDGF, TSP‐1, endostatin, and PF4 in platelets of healthy human subjects. In contrast to the highly variable levels in plasma and serum, the platelet‐derived measurements were accurate and reproducible with minimal biovariability. Am. J. Hematol., 2010. © 2010 Wiley‐Liss, Inc.     

Cytotoxic,antioxidative, genotoxic and antigenotoxic effects of <Emphasis Type="Italic">Horchata</Emphasis>, beverage of South Ecuador

Background

“Horchata” is an herbal mixture infusion consumed in Southern Ecuador; 66% of its plants are anti-inflammatory medicinal plant, and 51% are analgesics. Anti-inflammatory substances can prevent carcinogenesis mediated by cytotoxic effects and can prevent DNA damage. The aim of this study was to evaluate the cytotoxicity and apoptotic/antigenotoxic effects of horchata as well as its mechanism.

Methods

Nine different varieties of horchata were prepared in the traditional way and then freeze-dried. Phytochemical screening tested for the presence of secondary metabolites using standard procedures and antioxidant activities. The cytotoxic activity was evaluated on cerebral astrocytoma (D-384), prostate cancer (PC-3), breast cancer (MCF-7), colon cancer (RKO), lung cancer (A-549), immortalized Chinese hamster ovary cells (CHO-K1), and human peripheral blood lymphocytes via a MTS assay. The pro-apoptotic effects were evaluated with Anexin V/Propidium Iodide and western blot of Bax, Bcl-2, TP53, and TP73. Induction and reduction of ROS were assessed by fluorimetry. Genotoxic and antigenotoxic effects were evaluated with a comet assay and micronuclei on binucleated cells.

Results

Five of nine horchatas had cytotoxic effects against D-384 while not affecting normal cells. These horchatas induce cell death by apoptosis modulated by p53/p73. In CHO-K1 cells, the horchatas decrease the damage induced by hydrogen peroxide and Mitomycin C measured in the comet and micronucleus assay respectively.

Conclusions

The IC₅₀ range of effective horchatas in D-384 was 41 to 122 μg·mL^?1. This effect may be related to its use in traditional medicine (brain tonic). On the other hand, immortalized Chinese hamster ovary cells (CHO-K1) and lymphocytes did not show a cytotoxic effect. The most potent horchata induced apoptosis via a p53/p73-mediated mechanism.The horchatas present antigenotoxic properties, which may be related to the antioxidant capacity. Future studies on horchata components are necessary to understand the interactions and beneficial properties.

     

Intravitreal Bevacizumab for Photodynamic Therapy-Induced Massive Macular Detachment in Acute Central Serous Chorioretinopathy

We present a long followed up case of acute central serous chorioretinopathy (CSC) complicated by a severe visual loss due to massive pigment epithelium detachment of the macula after a full-dose photodynamic therapy (PDT). Rapid anatomical and functional improvement was observed after a single intravitreal injection of bevacizumab. To our knowledge, we report the first case of PDT-treated CSC complicated by severe visual loss. We can only speculate that the serous detachment of the posterior pole might have been caused by PDT-induced VEGF overexpression, explaining such an impressive response to Avastin treatment.Key Words: Bevacizumab, Central serous chorioretinopathy, Photodynamic therapy     

A lethal complication of papaverine-induced priapism

A large series of patients was treated for impotence with intracorporeal injections of papaverine and phentolamine with no major complications and no deaths reported. We report on a 45-year-old black man with advanced multiple sclerosis who died after such therapy. When the first self-administered injection of phentolamine and papaverine failed to produce an adequate erection the patient injected a second dose that resulted in priapism and death of massive pulmonary embolism.