Krūties piktybiniai navikai – viena svarbiausių sveikatos apsaugos problemų visame pasaulyje. Vėžiu ar kita piktybine liga sergantį pacientą turi nuolat stebėti gydytojas onkologas, o lygiagrečiai galima taikyti ir augalų terapiją, kadangi tai padidina chemoterapijos efektyvumą ir padeda sumažinti nepageidaujamą jos pašalinį poveikį. „Onkofit M“ receptūrą pasiūlė Prof. Dr. V. F. Korsun. Darbe aprašomas „Onkofit M“ preparatų (vaistažolių arbatos ir kietųjų kapsulių su sausaisiais augaliniais ekstraktais) technologijos kūrimas ir pateikti vaistinių augalinių žaliavų, įeinančių į “Onkofit M” sudėtį, aprašymai, farmakologiniai poveikiai, cheminės sudėtys, kurie pagrindžia pasirinkimą. Nustatyta, kad sausųjų augalinių ekstraktų mišinio technologinės savybės nepalankios kapsuliavimui, todėl jos suteiktos modeliuojant pagalbines medžiagas bei jų kiekius. Parinkta „Onkofit M“ kapsuliuojamos masės sudėtis. Teisingas mišinio sudėties parinkimas patvirtintas UAB „Aconitum“ – pagaminta eksperimentinė serija pilotiniam tyrimui. Patikrintas eksperimentinės serijos „Onkofit M“ kapsulių stabilumas. Parinkta placebo kapsuliuojamos masės sudėtis ir pagamintos pilotiniam tyrimui reikalingos placebo kapsulės. Paruoštas ir supakuotas į popierinius maišelius vaistažolių mišinys arbatai, vertintas jo stabilumas. / Malignant breast tumours – one of the most important health care issues in the world. A patient who is having a cancer must be constantly monitored by an oncologist and at the same type fitotherapy may be applied as well that can improve the efficiency of chemotherapy and reduce its side effects. The formula of “Onkofit M” has been introduced by V. F. Korsun. The development of the technology of “Onkofit M” preparations (herbal teas and solid capsules with dry extracts) description of herbal ingredients, pharmacological effects, chemical composition that validate the choice of certain components, are represented in this study. It has been identified that technological properties of dry plant extracts mixture are not suitable for capsulation; therefore they have been improved while varying types and amounts of additives. The proper composition of “Onkofit M” was selected and it was approved by UAB “Aconitum” – the experimental batch was manufactured for the pilot research. The stability of the experimental batch of “Onkofit M” capsules was tested. The composition of placebo capsules was determed and batch of such capsules was also manufactured for the pilot research. Herbal tea was prepared and packaged in paper bags; stability tests were performed as well.

OBJECTIVES: To determine if women with Human Immunodeficiency Virus infection with severe degrees of immunosuppression are more predisposed to mortality from Gestational Trophoblastic Disease compared with HIV-infected women with less severe degrees of immunosuppression and Human Immunodefiency Virus (HIV) non-infected women. DESIGN: Retrospective review of case records. METHOD: A retrospective review was performed on all patients with Gestational Trophoblastic from 2003 to July 2007. A chart review was conducted and information captured on a data sheet. This retrospective audit was performed at the combined gynaecology oncology clinic of Inkosi Albert Luthuli Central Hospital. All information was kept confidential and was strictly for the purposes of the audit. STATISTICS: Factors associated with mortality were tested using Fisher's exact test. Odds ratios were reported as a measure of the strength of association. Breslow-Day's test for homogeneity in odds ratios was used to compare mortality in HIV-infected and HIV non-infected women. The analysis was done using Stata 9. i RESULTS: A total of 78 patients with Gestational Trophoblastic Disease were reviewed. There were 53 patients with invasive molar pregnancy and 25 patients with choriocarcinoma. The HIV sero-prevalence was 31%. There were 15 deaths (19%). There were 8 HIV-infected (33%o) and 7 HIV non-infected (13%) women who demised. Of the 8 patients with CD4 counts less than 200 cells/ uL, 7 patients demised. There were no mortalities amongst patients with CD4 counts more than 200 cells/uL. Of the 15 deaths, 5 HIV-infected patients and 5 HIV non-infected patients received chemotherapy. There were 5 patients admitted in very poor general condition precluding the administration of chemotherapy. Amongst the 10 patients who received chemotherapy and demised, the causes of death included widespread disease, multiorgan failure and toxicity due to chemotherapy. CONCLUSION: The overall survival of all patients managed with Gestational Trophoblastic Disease was 82% in keeping with the expected high survival reported elsewhere. The majority of patients who demised were admitted in poor general condition and had abnormal blood profiles. Despite resuscitation, these patients failed to improve precluding the administration of chemotherapy which is the mainstay of treatment. Although the numbers are small, there is clear evidence that if patients are HIV-infected with CD4 counts 200 cells/uL despite transient grade 2 myelotoxicity. / Thesis (MMed)-University of KwaZulu-Natal, Durban, 2008.

BACKGROUND White vulva! skin lesions may be due to various conditions, including benign and non-benign causes. The dilemma faced by the clinician with such a patient is the aetiology of the lesion, as well as the approach to management. AIM To establish the aetiology of white vulva! skin lesions in patients attending the gynaecology clinic and to evaluate the role of Collin's test and vulvoscopy. SETTING R. K. Khan Hospital, which is a secondary level hospital in Durban, KwaZulu Natal. METHOD Sixty-two patients with white vulva! skin lesions whom consented to the study were recruited. The investigations consisted of Pap smear, colposcopy of the vulva [Vulvoscopy], perineum and where appropriate, vaginoscopy and colposcopy; Collin's test and biopsy of all abnormal areas detected by these tests. RESULTS Pruritus vulvae was the commonest presenting symptom [70%1. No vulvoscopic abnormalities were detected in 97% of patients, whilst 3% had acetowhite areas indicative of Human papilloma virus infection. Collin's test was positive in 40% of patients, although, histologically these areas were benign. All patients in the study had benign lesions on histology. CONCLUSION All patients in this study had benign causes of white vulval skin lesions. However, this cannot lead us to conclude that there is no role for doing Vulvoscopy and Collin's test, as premalignant and malignant lesions should be detected by these tests had they been present. / Thesis (M.Med.)-University of Natal, Durban, 1998.

Background: A compilation of high quality systematic reviews (SRs) on lifestyle factors associated with adult glioma and meningioma was developed. Methods and Materials: Phase 1 consisted of a systematic overview of existing SRs. For Phase 2, high quality SRs were incorporated in an update. Moderate or low quality SRs which had not been considered in a high quality review were eligible for a de-novo synthesis. Results: Phase 1 resulted in seven moderate to low quality reviews. From this, in Phase 2, smoking, mobile phone and hair dye use were subjected to de-novo reviews. For smoking, it was suggestive that past smokers had an increased risk. For mobile phone use, there was no overall association, however it was suggestive that ipsilateral and high cumulative call time were associated with slight increased risk. No association was observed for personal hair dye use. Conclusions: Despite these null associations, rigorous SR methods were used providing confidence in conveying these results.

Telomeres are nucleoprotein complexes located at the end of chromosomes. They have an essential role in protecting chromosome ends. Telomerase or ALT (alternative lengthening of telomeres) mechanisms maintain telomeres by compensating natural telomeric loss. We have set up a flow-FISH method and using mouse lymphoma cell lines we identified unexpectedly the presence of subpopulations of cells with different telomere lengths. Subpopulations of cells with different telomere lengths were also observed in a human ALT and non-ALT cell line. Differences in telomere length between subpopulations of cells were significant and we term this phenomenon TELEFLUCS (TElomere LEngth FLUctuations in Cell Subpopulations). By applying flow-FISH we could successfully measure telomere lengths during replicative senescence in human primary fibroblasts with different genetic defects that confer sensitivity to ionising radiation (IR). The results from this study, based on flow-FISH and Southern hybridisation measurements, revealed an accelerated rate of telomere shortening in radiosensitive fibroblasts. We also observed accelerated telomere shortening in murine BRCA1 deficient cells, another defect conferring radiosensitivity, in comparison with a BRCA1 proficient cell line. We transiently depleted BRCA1 by siRNAs in two human mammary epithelial cell lines but could not find changes in telomere length in comparison with control cells. Cytological evidence of telomere dysfunction was observed in all radiosensitive cell lines. These results suggest that mechanisms that confer sensitivity to IR may be linked with mechanisms that cause telomere dysfunction. Furthermore, we have been able to show that human ALT positive cell lines show dysfunctional telomeres as detected by either the presence of DSBs at their telomeres or cytogenetic analysis and usually cells with dysfunctional telomeres are sensitive to IR. Finally, we assessed hTERT mRNA splicing variants and telomerase activity in brain tumours, which exhibit considerable chromosome instability suggesting that DNA repair mechanisms may be impaired. We demonstrated that high levels of hTERT mRNAs and telomerase activity correlate with proliferation rate. The presence of hTERT splice variants did not strictly correlate with absence of telomerase activity but hTERT spliced transcripts were observed in some telomerase negative brain tumours suggesting that hTERT splicing may contribute to activation of ALT mechanisms.

The use of complementary non-invasive imaging modalities has been proposed to track disease progression, particularly cancer, while simultaneously evaluating therapeutic efficacy. A major obstacle is a limited ability to compare parameters obtained from different modalities, especially those from exogenous contrast agents or tracers. We hypothesize that combining Magnetic Resonance Imaging (MRI) and Ultrasound (US) will improve characterization of the tumour microenvironment. In this study, we describe a co-registration apparatus that facilitates the acquisition of a priori co-registered MR and US images in vivo. This apparatus was validated using phantom data and it was found that the US slices can be selected to an accuracy of +/- 100µm translationally and +/- 2 degrees rotationally. Additionally, it was shown that MRI and US may provide complimentary information about the tumour microenvironment, but more work needs to be done to assess repeatability of dynamic contrast enhanced MRI and US.

Abstract can be viewed in PDF document. / Thesis (M.Med.)-University of KwaZulu-Natal, Durban, 2010.

Laser thermal ablation (LTA) is an in situ ablative technique that induces heat destruction of liver tumours. Despite increasing clinical use of LTA, reports of long-term outcomes and limitation of treatment in specific cohorts of patients with liver tumours are lacking. In addition, the mechanisms of action of therapy have not been fully elucidated. This study highlights the long-term clinical results and limitations of LTA in the treatment of a cohort of patients with unresectable colorectal liver metastases and examines the mechanisms of action of thermal ablative injury in a murine model.

[Truncated abstract] A paradox exists in tumour immunology whereby progressive tumour growth exists in parallel with an anti-tumour T cell response. This defective T cell response is thought to result from the induction of T cell tolerance and/or tumour induced immunosuppression, which act to inhibit the activation, differentiation and function of tumour-specific CD8+ T cells. Dendritic cells (DCs) are professional antigen presenting cells (APCs) that are critical to the generation of effective CTL; however their function and phenotype is often defective or altered in tumour-bearing hosts, which may limit their capacity to mount an effective tumour specific T cell response. In this thesis, the role of DCs in the cross-presentation of tumour antigen was assessed in terms of their APC function, migration and location. In doing so the intention was to gain insight into the early processes that potentially contribute to the development of an ineffective anti-tumour immune response. This study examined cross-presentation of the nominal tumour antigen, influenza A hemagglutinin (HA) expressed by the murine malignant mesothelioma cell line, AB1-HA. Cross-presentation was predominantly restricted to the local draining lymph nodes throughout tumour growth and was mediated by CD8a+ and CD8a- DCs. This results in an ineffective CTL response due to the lack of DC activation and the presence of potentially immunosuppressive B7 molecules. However, the capacity of the CD8a- DC subset to cross-present antigen suggested a role for migratory tumour-resident DCs in this process. Analysis of tumour infiltrating DCs showed that they were paralysed in their capacity to cross-present tumour antigen and were immobilised at the tumour site. Conversely, cross-presentation of tumour antigen in the local draining lymph node was dependent on the continuous traffic of antigen from the tumour microenvironment. In this vein, small numbers of metastatic tumour cells were detected in the draining lymph nodes, however their isolation was dependent on the removal of DCs and T cells, suggesting immune control of metastatic spread. Thus, tumour cells may be the source of antigen for cross-presentation by DCs in the tumour draining lymph nodes. .... In conclusion, the results presented in this thesis support a role for DCs in the generation of tumour-specific T cell responses that fail to control tumour growth. In addition the results provide a basis for further investigation into the effects of chemotherapy on the source and form of tumour antigen for cross-presentation by specific DC subsets in the tumour bearing host. These findings may have important implications for the development of future anti-cancer immune therapies targeting DCs.

Introduction: Radiofrequency ablation (RFA) is a popular method of treating unresectable liver tumours by the use of a high frequency, alternating electrical current that heats and destroys tumour cells. The size of the ablation is limited by localised charring of adjacent tissue that prevents further conduction of the radiofrequency current. In the clinical setting, this results in increased rates of local recurrence in tumours that are greater than 3 cm in diameter as multiple, overlapping ablations need to be performed to treat the one tumour. To overcome this problem, a modified form of RFA called Bimodal Electric Tissue Ablation (BETA) has been created. BETA adds a direct electrical current to the alternating radiofrequency current, thus establishing its bimodal character. When direct currents are used in biological tissues, water is transferred from anode to cathode by a process called electro-osmosis. By attaching the cathode to the radiofrequency electrode, water is attracted to the area thus preventing tissue desiccation and charring. The BETA circuit has been constructed and tested using a porcine model. The aims of the studies are to confirm that larger ablations can be produced with the BETA system and that it is safe to use in an animal model. Three studies have been performed to test these aims in porcine liver. Methods: The first study was designed to compare sizes of the ablation produced between standard RFA and the BETA circuit. This was followed by a long-term study to assess associated changes to liver function and pathological changes within the liver as well as identifying any other treatment related morbidity. The third study assessed the difference in ablation size and safety aspects when the positive electrode of the direct current circuitry was moved from small surface area under the skin to a large surface area on the skin. Results: Ablations with significantly larger diameters are created with the BETA circuit using a multi-tine needle (49.55 mm versus 27.78 mm, p<0.001). This finding was confirmed in the third experiment using a straight needle (25 mm versus 15.33 mm, p<0.001). Ablations produced by the BETA circuit induce coagulative necrosis within the treated liver and the injury heals by fibrosis in a manner similar to other thermal therapies. Significant rises in some serum liver enzymes are seen within 24 hours of treatment but these return to normal within 4 days. An electrolytic type injury can be produced at the site of the positive electrode. By increasing the surface area of this electrode, the risk of tissue damage is decreased but ablations are significantly smaller (18 mm versus 25 mm, p<0.001). Conclusions: The BETA circuit consistently produces significantly larger ablations than RFA. The treatment appears safe but positioning of the positive electrode of the direct current requires careful consideration. Injuries produced behave like other thermal therapies with coagulative necrosis followed by fibrotic healing. As larger ablations are consistently produced, it is hypothesised that with further refinements, tumours greater than 3 cm in diameter could be treated with lower rates of recurrence. / Thesis (M.S.) -- University of Adelaide, School of Medicine, 2008