Long-term stabilization of stage 4 colon cancer using sodium dichloroacetate therapy

Oral dichloroacetate sodium(DCA) has been investigated as a novel metabolic therapy for various cancers since 2007, based on data from Bonnet et al that DCA can trigger apoptosis of human lung, breast and brain cancer cells. Response to therapy in human studies is measured by standard response evaluation criteria for solid tumours definitions, which define "response" by the degree of tumour reduction, or tumour disappearance on imaging. However, Blackburn et al have demonstrated that DCA can also act as a cytostatic agent in vitro and in vivo, without causing apoptosis(programmed cell death). A case is presented in which oral DCA therapy resulted in tumour stabilization of stage 4 colon cancer in a 57 years old female for a period of nearly 4 years, with no serious toxicity. Since the natural history of stage 4 colon cancer consists of steady progression leading to disability and death, this case highlights a novel use of DCA as a cytostatic agent with a potential to maintain long-term stability of advanced-stage cancer.

Norsesquiterpenoids from the leaves of Croton tiglium

Two new compounds,badounoids A(1)and B(2),together with 13 known norsesquiterpenes,were isolated from the leaves of Croton tiglium L.The structures of the new compounds were established by means of spectroscopic methods.The absolute configuration of badounoid B was determined by single-crystal X-ray diffraction analysis.All the known compounds were isolated from Croton plants for the first time which added a new chemical facet for this genus.The selected compounds were evaluated for their cytostatic activity against several cancer cell lines.None of them was found to be active.

Tumor cell death visualization of renal cell carcinoma under the combined effect of the Gratiola officinalis extract and cyclophosphamide using fluorescent staining methods

Objective of the study:We used fluorescence imaging methods of apoptosis and necrosis in human renal carcinoma A498 tumor cells in vitro to reveal the indicated forms of cell death under the combined effect of flavonoid-containing extract of Gratiola officinalis and cytostatic(cyclo-phosphamide).Materials and methods:The dyes were propidium iodide and acridine orange,which were used in the"alive and dead"test.This test helped us to identify the total number of dead cells in the forms of necrosis and apoptosis and the number of cells in which apoptosis had started,it was characterized by the appearance of apoptotic bodies or nucleus pyknosis.Results:We found the most pronounced cytotoxic activity at the ratio of extract of Gratiola officinalis and cyclophosphamide concentrations of 1∶1.The number of living cells decreased when exposed to the ratio of extract and cytostatic concentrations of 2∶1.When the ratio of concentration of the extract relative to the cytostatic increased to 3∶1,the cytostatic activity of the extract began to appear,the total number of tumor cells decreased.The number of cells with nucleus pyknosis and the number of cells with apoptosis signs significantly increased at a 3∶1 ratio of extract and cytostatic concentrations,which confirms the presence of pro-apoptotic activity of the studied combination.This trend indicates the dependence of a certain form of cell death(apoptosis,necrosis)on the ratio of extract and cytostatic doses,and it also demon-strates the cytostatic and cytotoxic effects of this combination.Conclusion:Fluorescence methods of investigation in the"alive and dead"test allowed us to visualize the forms of cell death of human kidney carcinoma A498 by combined exposure to the fiavonoid-containing extract of Gratiola officinalis and cytostatic(cyclophosphamide)24 h after exposure.We found that the combination with a concentration ratio of the extract and cyclophosphamide of 3:1 has the greatest effectiveness due to stimulation of the cytostatic effect and cytotoxic effect.

Long-term stabilization of metastatic melanoma with sodium dichloroacetate

Sodium dichloroacetate(DCA) has been studied as a metabolic cancer therapy since 2007, based on a publication from Bonnet et al demonstrating that DCA can induce apoptosis(programmed cell death) in human breast, lung and brain cancer cells. Classically, the response of cancer to a medical therapy in human research is measured by Response Evaluation Criterial for Solid Tumours definitions, which define "response" by the degree of tumour reduction, or tumour disappearance on imaging, however disease stabilization is also a beneficial clinical outcome. It has been shown that DCA can function as a cytostatic agent in vitro and in vivo, without causing apoptosis. A case of a 32-year-old male is presented in which DCA therapy, with no concurrent conventional therapy, resulted in regression and stabilization of recurrent metastatic melanoma for over 4 years' duration, with trivial side effects. This case demonstrates that DCA can be used to reduce disease volume and maintain longterm stability in patients with advanced melanoma.

Enhancement of Sister Chromatid Exchanges (SCEs) in Peripheral Blood Lymphocytes of Women with Polycystic Ovary Syndrome (PCOS) <i>in Vitro</i>

The aim of the present study was to determine the level of underlying DNA damage in females with PCOS. Twenty-two women with PCOS and twenty-two healthy controls were included in this study. Patients were further categorized into three phenotypic subgroups: Subgroup A, oligo/anovulation (ANOV) and polycystic ovaries (PCO);Subgroup B, hyperandrogenism (HA) as a main characteristic (HA + ANOV or HA + PCO);Subgroup C, all three conditions present (HA + ANOV + PCO). The frequency of sister chromatid exchanges (SCEs) was used as an index of cytogenetic damage. Proliferation rate index (PRI), mitotic index (MI), average generation time (AGT) and population doubling time (PDT) were also evaluated. A significant (p < 0.01) increase in SCE levels along with a significant (p < 0.01) reduction in PRIs and MIs were observed in women with PCOS compared with healthy subjects. Additionally, subgroup C demonstrated statistically significant differences compared with others, while subgroup A had similar results with healthy females. Our results suggest that females with PCOS show increased chromosomal instability in peripheral lymphocytes and a consequent inability of the cells to promote their own mitotic cycle. A positive correlation between DNA damage and PCOS phenotypes is also reported.

A Case Report on Canine Transmissible Venereal Tumor

A male Japanese spitz(3 years)was brought at Himalayan Animal Rescue Trust(HART),Pokhara with a complaint of swollen gums and loss of appetite.A lobulated tumorous mass was seen at the gingival region on physical examination.Diagnosis and treatment of condition detected in the dog was the major objective.Impression smear of tumor cell was prepared and was observed under oil immersion microscope(100x).Microscopic examination shows the presence of vacuolations within the cytoplasm and the condition was diagnosed to be CTVT.Chemotherapy was performed using the most effective cytostatic agents I.e.Vincristine sulphate(once a week,I/v).The chemotherapy was repeated for 3 doses till the tumor gets completely regressed.The condition was resolved after third session of chemotherapy.Myelosuppression and gastrointestinal effects like vomiting are the major complications of using vincristine.

Cytotoxicity of new Ho(Ⅲ) and Pr(Ⅲ) complexes

New complexes of coumarin-3-carboxylic acid(HCCA) with Ho(Ⅲ) and Pr(Ⅲ) were synthesized and their structures and spectral properties were investigated by elemental analysis,IR,Raman and NMR measurements.According to the experimental data the complexes' formula and geometries were suggested.Vibrational frequencies,IR intensities and Raman activities as well as 1H NMR chemical shifts of HCCA and its Ho(Ⅲ) and Pr(Ⅲ) complexes were presented.The comparative experimental vibrational and NMR analyses of both the ligand and the Ln(Ⅲ) complexes predicted the bidentate binding to Ho(Ⅲ) and Pr(Ⅲ) through the deprotonated carboxylic oxygen and the carbonylic oxygen of the ligand.The cytotoxic/cytostatic properties of the ligand and the newly synthesized complexes of coumarin-3-carboxylic acid with Ho(Ⅲ) and Pr(Ⅲ) were tested by MTT reduction assay against two mouse tumor cell lines:melanoma B16 and fibrosarcoma L929.They were also tested for cytotoxicity against normal mouse peritoneal macrophages.The proliferation inhibitory effect of the complexes compared to that of the ligand proved their cytotoxic/cytostatic properties against both the tumor cell lines.In addition,the complexes were less cytotoxic against normal mouse macrophages and were able to modulate NO release by activated macrophages.The obtained results were in accordance with our previously published data concerning the activity of lanthanide(Ⅲ) complexes with other coumarin derivatives.