Curative-Intent Radiotherapy for Squamous Cell Carcinoma of the Head and Neck in Sri Lanka: The Impact of Radiotherapy Technique on Survival.

AIMS: We conducted a retrospective analysis of patients with squamous cell carcinoma of the head and neck (SCCHN) treated with curative-intent radiotherapy at the National Cancer Institute of Sri Lanka to determine the impact of the treatment technique on disease-free survival (DFS). MATERIALS AND METHODS: SCCHN patients treated with radical radiotherapy or adjuvant postoperative radiotherapy from 2016 to 2017 were included in the study. Data on the following variables were collected by reviewing clinical and radiotherapy treatment records: age, gender, tumour site, stage, time to delivery of radiotherapy, use of neoadjuvant chemotherapy, use of concurrent radiosensitising chemotherapy and treatment technique. DFS, defined as the time to death, tumour recurrence or loss to follow-up, was the primary end point and outcomes were compared between patients treated with intensity-modulated radiotherapy (IMRT) in linear accelerators and those treated with conventional radiotherapy in cobalt teletherapy units. Univariate and multivariate analyses were carried out on known prognostic variables. RESULTS: In total, 408 patients were included in the study, with 138 (34%) being treated with IMRT in the linear accelerator. More than 75% of patients were of stage III or IV at diagnosis. The 2-year DFS of the whole cohort was 25% (95% confidence interval 21-30%). Patients treated with IMRT in the linear accelerator had a superior DFS in comparison with those treated with conventional radiotherapy in the cobalt teletherapy units (P < 0.001, hazard ratio 0.64, 95% confidence interval 0.5-0.82). Higher stage, cobalt treatment and use of neoadjuvant chemotherapy were adversely associated with DFS on multivariate analysis. CONCLUSION: A large proportion of patients with SCCHN treated with curative-intent radiotherapy in Sri Lanka had locally advanced disease and DFS was superior in patients treated with IMRT in the linear accelerator.

Reduction of Dinitrogen to Ammonia and Hydrazine on Low-Valent Ruthenium Complexes.

The ruthenium(0) dinitrogen complexes [Ru(N2)(PP3R)] [PP3R = P(CH2CH2PR2)3; R = iPr or Cy] react with triflic acid and other strong acids to afford mixtures of ammonia and hydrazine. In this reaction, Ru(0) is oxidized to Ru(II), and depending on the solvent, Ru(II) benzene or triflate complexes are isolated and characterized from the reactions with triflic acid as the final metal-containing products from the reaction. The Ru(II) products are isolated and reduced back to Ru(0) dinitrogen complexes providing a cycle for the reduction of coordinated dinitrogen.

Country Report: The Report of Transplant Activity and Outcome During the First 12 Months at the First National Hematopoietic Stem Cell Transplant Center in Sri Lanka.

Sri Lanka is a developing country with a population of 21 million. Nation Cancer Institute (NCI) is the largest tertiary cancer centre with universal health coverage. Absence of hematopoietic stem cell transplant (HSCT) was a major deficiency as most patients cannot afford transplant abroad. In 2013-14, NCI decided to establish the first National HSCT center in collaboration with St. Vincent's Hospital Sydney. Eventually, the first Autologous HSCT was established at NCI in December 2016. Patients with multiple myeloma (MM) in very good partial remission or better remission, and patients with relapsed Non-Hodgkin's lymphoma (NHL) and Hodgkin lymphoma (HL), who were less than 65 years with good performance status were selected. Stem cells were mobilized with cyclophosphamide and G-CSF and the products were cryopreserved. Melphalan was the conditioning regime for MM while BEAM was used for HL and NHL. Twenty autologous transplants were performed in the first year. Mean age was 47 years (range: 17-62) and male to female ratio was 3: 2. There were 17 MM and one each of NHL, HL and POEMS syndrome patients. Median CD34＋ stem cells collected was 12.72×106/kg (range: 3-31) and median infused cell dose was 4.07×106/kg (range: 2-7.4). Median engraftment day was 13 (range: 11-19) and median hospitalization was 16 days (range: 14-20). All developed febrile neutropenia and GradeⅢ thrombocytopenia. Zero transplant-related mortality was observed with acceptable morbidity. At the median follow-up of 47 weeks, the overall survival was 100% with all the patients still in remission.

Antibacterial Activity of some Medicinal Mangroves against Antibiotic Resistant Pathogenic Bacteria.

The antibacterial activity of the leaves and bark of mangrove plants, Avicennia marina, A. officinalis, Bruguiera sexangula, Exoecaria agallocha, Lumnitzera racemosa, and Rhizophora apiculata was evaluated against antibiotic resistant pathogenic bacteria, Staphylococcus aureus and Proteus sp. Soxhlet extracts of petroleum ether, ethyl acetate, ethanol and water were prepared and evaluated the antibacterial activity using agar diffusion method. Most of the plant extracts showed promising antibacterial activity against both bacterial species. However, higher antibacterial activity was observed for Staphylococcus aureus than Proteus sp. The highest antibacterial activity was shown by ethyl acetate of mature leaf extracts of E. agallocha for Staphylococcus aureus. All ethyl acetate extracts showed higher inhibition against S. aureus while some extracts of chloroform, ethyl acetate and ethanol gave inhibition against Proteus sp. None of the petroleum ether and aqueous extracts showed inhibition against Proteus sp. All fresh plant materials did also show more antibacterial activity against both bacterial strains than did dried plant extracts. Antibacterial activity of fresh and dried plant materials reduced for both bacterial strains with time after extraction. Since L. racemosa and A. marina gave the best inhibition for bacterial species, they were used for further investigations. Charcoal treated plant extracts of L. racemosa and A. marina were able to inhibit both bacterial strains more than those of untreated plant extracts. Phytochemical screening of mature leaf, bark of L. racemosa and leaf extracts of A. marina has been carried out and revealed that leaf and bark contained alkaloids, steroids, triterpenoids and flavonoids. None of the above extracts indicate the presence of saponins and cardiac glycosides. Separated bands of extracts by TLC analysis showed antibacterial activity against S. aureus.

Inclusion complexes of the antitumour metallocenes Cp(2)MCl(2) (M = Mo, Ti) with cucurbit[n]urils.

The encapsulation of the aquated forms of molybdocene dichloride and titanocene dichloride by cucurbit[n]uril (Q[n], where n = 7 and 8) at different pD values has been studied by (1)H NMR spectroscopy and molecular modelling. (1)H NMR titration experiments indicate that both metallocenes form 1 : 1 host-guest complexes with both Q[7] and Q[8]. In these complexes, both the cyclopentadienyl ligands and metal centre are positioned deep within the cucurbituril cavity. In vitro cell proliferation studies using the cancer cell lines MCF-7 and 2008 showed that the encapsulated molybdocene complex was more active than the corresponding free metallocene, with GI(50) values of 210 and 400 muM respectively. However, unexpectedly the encapsulation of Cp(2)MoCl(2(aq))at pD 7 catalysed significant degradation of the cucurbituril framework in the presence of oxygen. Encapsulation of Cp(2)TiCl(2(aq)) by Q[7] greatly slowed the protonolysis of the cyclopentadienyl ligands in aqueous phosphate buffer (pD 7), while encapsulation in Q[8] only slightly retarded the hydrolytic degradation of the metallocene.

Antitumour bis(cyclopentadienyl) metal complexes: titanocene and molybdocene dichloride and derivatives.

This Perspective will focus on recent developments in the field of antitumour metallocenes structurally related to titanocene dichloride. Despite extensive testing of titanocene dichloride which culminated in phase I and II clinical trials, further trials have been abandoned. While DNA has been implicated as the major target related to anticancer activity, identification of the active species and mechanism of action has been poorly understood and hence the design of second generation titanocene derivatives has not been possible. Recent mechanistic studies have provided a plausible mechanism for delivery of Ti to cancer cells via transferrin mediated endocytosis. This mechanism requires the presence of labile Cp-Ti bonds that hydrolyse on a time scale to deliver Ti to transferrin. A large range of titanocene derivatives in which the cyclopentadienyl rings have been substituted by both electron withdrawing and donating groups, including aromatic, alkyl and cyclic amines, have been prepared and tested for activity in the last 5 years. These results have shown that subtle structural effects can have a significant effect on biological activity and that biological activity is highly cell line dependent. However, the biological chemistry and cellular studies required to determine the mechanism of action of these new titanocenes have not been reported. In contrast, the bioorganometallic chemistry and cellular studies of molybdocene dichloride have implicated interaction with cellular thiols as the key reaction related to biological activity. Tailoring of the pseudohalide ligands by tuning the strength of the Mo-S bonds provides the opportunity to enhance cell uptake. Further research is required to establish the origin of antitumour activity.

Trehalose induces antagonism towards Pythium debaryanum in Pseudomonas fluorescens ATCC 17400.

Pseudomonas fluorescens ATCC 17400 shows in vitro activity against Pythium debaryanum under conditions of iron limitation. A lacZ reporter gene introduced by transposon mutagenesis into the P. fluorescens ATCC 17400 trehalase gene (treA) was induced by a factor released by the phytopathogen Pythium debaryanum. The induction of the lacZ gene was lost upon treatment of the Pythium supernatant with commercial trehalase. A trehalose concentration as low as 1 microM could induce the expression of treA. The mutation did not affect the wild-type potential for fungus antagonism but drastically decreased the osmotolerance of the mutant in liquid culture and suppressed the ability of P. fluorescens ATCC 17400 to utilize trehalose as a carbon source. A subsequent transposon insertion in treP, one of the trehalose phosphotransferase genes upstream of treA, silenced the lacZ gene. This double mutant restricted fungal growth only under conditions of high osmolarity, which probably results in internal trehalose accumulation. These data confirm the role of the disaccharide trehalose in osmotolerance, and they indicate its additional role as an initiator of or a signal for fungal antagonism.