Krebswissenschaft und -therapie

Urinary bladder cancer (UBC), which rinks ninth in worldwide cancer incidence, is a type of malignant growth of abnormal cells. UBC can be caused by: (A) Inhalation of cigarette smoke, smoke from cooking fume hoods, industrial/environmental carcinogens, volatiles of coal tar, and diesel exhaust. (B) Drugs such as cyclophosphazine, chloronaphazine, phenacetin, nitrosamines, and herbal remedies like aristolochic acids. (C) Contact of chlorinated water or hair dyes. (D) Ingestion of bracken fern (Pteridium aquilinum) and/or arsenic.E.Infections of Schistosoma haematobium (schizosomiasis), Enterobacteria (Cystitis) and Papilloma viruses. F.Endogenous carcinogens such as tryptophan metabolites and other amines.G.Hereditary factors such as acetylator of the N-acetyltransferase, and mutations or malfunction of oncogenes/suppressor genes. Prevention of bladder cancer should include cessation of smoking, minimization of exposure to cooking fumes, and elimination of industrial and environmental carcinogens. Other measures worth considering include: (A) Intake of fruits, vegetables, soy products, vitamins, green tea, and decrease of fat consumption. Ingestion of food that isrich in selenium, garlic, lycopene, linoleic acid, various vitamins, gallic acid, and betulinic acid, etc. (B) Intake of non-nutritional factorsincluding astaxanthin, procatachuic, diosmin, hesperidin, 1,4-phenylene diisothiocyanate, crytoxanthin, indomechacin, and silibinin, etc. (C) Administration of drugs such as difluoromethylornithine (DFMO), no steroid anti-inflammatory drugs (NSAIDs), astorvastatin, oitipraz, and Bacillus Calmette-Guerin (BCG). Retinoic acid in combination with ketoconazole was reported to be helpful to bladder cancer patients. In conclusion, the management of interplay of multiple factors of cause, cure and prevention, is the major concern of UBC.

Rhabdoid meningioma is a rare subtype of meningiomas accounting for 1-3% of all intracranial meningiomas and classified as WHO Grade III tumor. It has an aggressive course and needs to be treated by both surgery and radiotherapy. Here we present a rare case of rhabdoid meningioma in a 24 year old lady with complaints of focal seizures, paresis and diplopia. CT & MRI showed a mass attached to dura in left posterosuperior frontoparietal region with peripheral edema. Histopathology showed large tumor cells arranged in sheets, whorls and papillary pattern. The patient was treated by surgery followed by radiation. This is reported to aware the surgical pathologists to keep this subtype as a differential diagnosis while interpreting any meningioma as it has an aggressive course.

Alternative remedies for cancer treatment is a multi-billion dollar industry. In particular, breast cancer (BC) patients use alternative and natural remedies more frequently than patients with other malignancies. Propolis is an example of a honeybee-produced naturopathic formulation, contents of which differ by geographic location. It is readily available, affordable, and in use safely since ancient times globally. Caffeic acid phenethyl ester (CAPE) is a major active component in propolis and is thought to be responsible for its varied properties, including antibacterial, antiviral, antifungal, antioxidant, anti-inflammatory and anticancer. CAPE is effective in many models of human cancer, including BC as we have previously shown. CAPE affects genes associated with tumor cell growth and survival, angiogenesis and chemoresistance. We demonstrate that these are related in part to CAPE’s role as a histone deacetylase inhibitor, a class of drugs designated as epigenetic agents that modulate the activities of oncogenes and tumor suppressor genes. CAPE and propolis, cause an accumulation of acetylated histone proteins in MCF-7 (ER+) and MDA-MB-231 (ER-/PR-/Her2-) cells with associated decreases in ER and PR in MCF-7 cells, and upregulation of ER and decrease in EGFR in MDA-231 cells. In addition, these products reduced activated phosphorylated Her 2 protein in SKBR3 (Her 2 +) cells. Interestingly, propolis, when normalized for CAPE content, appears to be more potent than CAPE alone similarly to the greater effects of complete foods than isolated components. These data provide a potential mechanistic basis for one of the oldest naturopathic agents used in medicine and cancer treatment.

Introduction: Vitamin C (VC), Vitamin K3 (VK3) and the combination (VC:VK3) were evaluated against human bladder cancer cell lines RT-4 and T24 to evaluate their synergistic anticancer activity.

Methods/Results: An MTT assay compared a 1hr pulsed versus a 5hr continuous exposure. VC:VK3 was synergistic, increasing the antitumor activity 12- to 24 fold for RT-4 cells. VC:VK3 pulsed versus continuous exposure produced comparable CD50 values, indicating a triggered response involving a catalase reversible redox mechanism generating hydrogen peroxide. Hydrogen peroxide production caused lipid peroxidation and depletion of cellular thiols. ATP levels were measured over 5hrs to determine metabolic effects where VC:VK3 caused a unique spike in ATP levels. Though the cause of the ATP spike is unknown a possible mechanism is a shunt formed around a defective region of complex III of the ETC from coenzyme Q to cytochrome c, producing a shift from glycolytic to oxidative metabolism and a diminution of lactic acidosis. Analysis of mitochondrial and extra mitochondrial calcium levels revealed a unique calcium pattern for RT4 cells treated with CD90 doses of VC, VK3 or VC:VK3.

Conclusion: VC:VK3 was able to cause autoschizic cell death through oxidative stress, thiol depletion, lipid peroxidation, modification of ATP levels and calcium regulation. Because of these results, VC:VK3 was granted orphan drug status for the treatment of metastatic or locally advanced, inoperable transitional cell carcinoma of the urothelium (stage III and IV bladder cancer). Efforts are underway to conduct a phase II clinical trial for this indication.

Background: Patients with prostate cancer who accede to radiation therapy usually experience several side effects and these toxicities are sometimes dose limiting. Some previous in vitro and in vivo studies have proposed a radioprotective role for curcumin, the yellow pigment of turmeric.

Objectives: The purpose of this investigation was to assess the radioprotective effects of curcumin supplementation in patients with prostate cancer.

Methods: Forty prostate cancer patients undergoing external beam radiotherapy (EBRT) were randomly assigned to curcumin group, taking 3 g/d curcumin (6 × 500 mg capsules of BCM95 n=20), or placebo group (n=20). Quality of life was assessed by the Persian version of the European Organization for Research and Treatment of Cancer prostate cancer-specific quality of life questionnaire (QLQ-PR25).Analysis of covariance was used to compare radiotherapy related symptoms between groups following the intervention, adjusted for baseline symptoms.

Results: No differences in urinary symptoms, bowel symptoms, treatment related symptoms and sexual activity were observed between the curcumin and placebo groups before the intervention. The change in urinary symptoms across the 20-week period differed significantly between groups (p=0.011) and patients in the curcumin group experienced much milder urinary symptoms compared with the placebo group. No group differences were observed in any other domain of the QLQ-PR25.

Conclusions: Curcumin can confer radioprotective effect in patients with prostate cancer who undergo radiation therapy through reducing the severity of radiotherapy related urinary symptoms. However supplementation with 3 g/ day curcumin could not reduce the severity of bowel symptoms or other treatment related symptoms.