Krebswissenschaft und -therapie

Recent proteomic studies identified Transferin (TF) as a potential colon cancer biomarker. A dipstick TF test similar to Immuno Fecal Occult Blood Test (IFOBT) was developed, and an initial study showed the TF test had compatible performance characteristics for detecting colon cancer and adenoma. The goal of this study was to evaluate the efficacy of the combination of TF and IFOBT for detecting advanced adenomas and cancer in asymptomatic and symptomatic populations. A total of 1,943 healthy subjects (asymptomatic group) and 201 subjects with various gastrointestinal symptoms (symptomatic group) were recruited for the study. For asymptomatic subjects, one fecal sample was collected for concurrent TF and IFOBT testing. Colonoscopy was performed for individuals positive for either TF or IFOBT. For the symptomatic subjects, each individual underwent TF, IFOBT, and colonoscopy simultaneously. For asymptomatic group, 1,737 individuals tested for TF and IFOBT, 251 subjects (14.5%) showed either TF or IFOBT positivity. Colonoscopy was performed for 193 of the 251 individuals. A total of 3 colorectal cancers and 43 advanced adenomas were detected. Combination of the two tests (either/or) significantly increased the detection rate for colorectal cancers and advanced adenomas compared to IFOBT alone (2.6% vs. 1.6%, P=0.034). In the symptomatic group, the combined test also significantly increased the sensitivity for detecting advanced adenomas and cancer than that of IFOBT alone (77.9% vs. 55.9%, P=0.006), but with decreased specificity (42.1% vs 63.9%, P=0.005). Combined TF and IFOBT test increased the detection rate of colorectal adenoma and cancer in both asymptomatic and symptomatic populations.

Malignant mesothelioma of the peritoneum is rather unusual and is only 10-20% of malignant mesothelioma. Malignant mesothelioma is pleural recognized by its location. The etiology of malignant mesothelioma is in 80% of cases prior contact with asbestos but there are cases without specific cause. The prognosis for MPM is poor with median survival of 5.4 months versus 12.5 months for pleural mesothelioma. The diagnosis of MPM is often difficult and requires surgical biopsies by laparoscopy or laparotomy or ascitic cytology. A surgical cytoreduction combined with hyperthermic intraperitoneal chemotherapy is the best therapeutic approach for MPM but unfortunately often advanced disease at diagnosis. We must therefore resort to systemic chemotherapy based on platinum or symptomatic treatments.

Aim of the study: This work aims to search for markers suitable for the screening of bladder cancer, which should be specific, sensitive, reproducible, non-invasive and at acceptable cost.

Patients and methods: The study included 45 patients diagnosed as bladder cancer (30 TCC, 15 SCC) of different stages and grades, 20 patients with various urothelial diseases, besides 15 healthy volunteers of matched age and sex to the malignant group. A random midstream urine sample was collected in a sterile container for the determination of telomerase by RT-PCR, keratin 20 by RT-PCR and immunohistochemical staining, urine cytology in addition to DNA dielectric properties.

Results: All parameters (telomerase, K20, cytology and DNA dielectric properties) for the malignant group showed significant difference from both the benign and the control groups. With respect to the grade, only K20 showed a significant positive correlation with grade in both TCC and SCC.

Conclusion: K20 is the best candidate as screening test for the diagnosis of bladder cancer, representing the highest sensitivity and specificity, beside the radiological and histopathological studies.

As a method, RT-PCR is superior to immunostaining for the detection of bladder cancer, meanwhile K20 immunohistochemistry (IHC) results were much better than urine cytology as a bladder cancer screening test. Haematuria and inflammation reduced the specificity of telomerase assay, which reduced its validity as a tumor marker of bladder cancer. The studied DNA has a dielectric dispersion in the frequency range used. There is change in the electric properties of DNA of bladder cancer patients. The dielectric properties of DNA may be used as valuable supplementary markers in diagnosis of bladder cancer.

Thyroid hormone and Estrogen regulate transcription(s) of target genes by binding to their nuclear receptors that interact with specific responsive elements -TRE and ERE, respectively. Recently, we have demonstrated that 3, 3’5 Triiodo L Thyronine (T₃) can induce apoptosis in ER positive breast cancer cells (MCF-7) through downregulation of Senescence Marker Protein-30 (SMP30) gene. SMP30, a novel age-associated protein which decreases during ageing is highly expressed in hepatocytes and in renal tubular epithelia. Earlier reports suggest that SMP30 too plays a diverse role in proliferation, survival and differentiation of the cells. SMP30 has also been reported to be downregulated by 17β-Estradiol (E₂) in prostate gland and mammary epithelial cells. Interestingly, Thyroid Receptors (TRs) and Estrogen Receptors (ERs) share a common consensus half site sequence. In this context; we hypothesize a possible competition between both the receptors in SMP30 promoter under different types of hormonal signaling. To prove this hypothesis, gel retardation and luciferase assays were conducted by taking hSMP30 promoter reporter constructs which validated our findings for the putative ERE site. Competition Chromatin Immunoprecipitation Assay (ChIP) in the above mentioned ERE showed differential TRβ binding upon thyroid/estrogen hormone treatment, while ERα showed binding mainly in control and estrogen treated sample. Although the SMP30 promoter activity was almost same in response to E₂ and T₃, but the functional consequences of down regulation of SMP30 in human breast cancer cells post E₂/T₃ treatment were different in terms of apoptosis. To unravel the mechanism behind the differential consequences of E₂/T₃ treatment, in addition to looking at the expression of regular apoptotic markers such as Bax and Cleaved PARP, we have also tried to verify the possible involvement of p53, which has been already reported to be a downstream target of SMP30.

Cancer is fast growing out of the reach of trained oncologists and other experts. It was once thought to be a problem almost exclusive to the developed world but cancer is now a leading cause of morbidity and mortality in developing (resource-limited) countries thus making it a health priority. The need to deliver cancer care in resourcelimited settings is gaining urgency, with need for particular emphasis on the creation of cost-effective, rational algorithms utilizing affordable chemotherapeutics to treat curable disease. The delivery of comprehensive cancer care in resource-poor settings demands a concerted effort by a team of multidisciplinary care providers, even if they are not trained oncologists. This article seeks to highlight the challenges in managing cancers in the developing world using Nigerian Christian Hospital experience as an example. We suggest ways of improving the care of cancer patients in such settings.

Melanoma is the most aggressive form of skin cancer. Developments in melanoma basic research and therapeutic interventions have advanced tremendously with help of animal models of this disease. Transgenic and knockout mice have provided a wide array of melanoma models, which are primarily used for studying molecular pathways and developing treatment strategies. To the best of our knowledge, there has been no natural animal model for research on chemoprevention of melanoma induced by UV light alone. In this editorial, we discuss the potential of the laboratory opossum (Monodelphis domestica) as a natural model for research on chemoprevention of melanoma.