Expression of IAP family proteins and its clinical importance in breast cancer patients.

Inhibitor of apoptosis (IAP) family proteins is involved in mechanisms of resistance to apoptosis in various cancer cells. The aim of this study was to assess the expression of selected IAP proteins such as XIAP, cIAP-1, cIAP-2 and survivin in breast cancer patients and evaluates their relationship with the prognostic and predictive factors and their impact to overall survival (OS) and progression free survival (PFS). The study was conducted with the use of tissue samples prospectively collected from 92 previously untreated female breast cancer patients. The control encompassed 10 fibroadenoma patients. The expression of XIAP, cIAP-1, cIAP-2 and survivin was assessed using flow multicolor cytometry. XIAP expression was present in 99 % of the breast cancer patients (91/92) with the median expression 13.65% (range 1-66.8%). Expression of XIAP in breast cancer was significantly higher compared to the control group (p=0.006). Median expression of cIAP-1, cIAP-2 and survivin in the study group was 25.95% (range 0.8-83.7%), 16.7% (range 1-53.2%) and 4.6% (range 0-43%) respectively. In the rank Spearman test, strong correlations (p<0.001) were seen among the expressions of XIAP, cIAP-2 and survivin, in all combination. Additionally, week correlation between XIAP and cIAP-1 was observed (p=0.02). The median expression of XIAP and survivin was significantly higher in more advanced tumors (stages pT2/pT3 vs. pT1). The median PFS and OS in breast cancer group were 46.15 and 47.1 months respectively. No significant correlations were observed among expressions of IAP family proteins and survival. However, low expression of XIAP in breast cancer showed trend to longer PFS (p=0.08). XIAP, cIAP-1 cIAP-2 and survivin participate in antiapoptotic mechanisms in breast cancer and XIAP and survivin seem to have the most significant prognostic importance. Further studies are needed to establish more complete prognostic and predictive values of IAP family proteins in breast cancer patients.

Correlation of Smac/DIABLO protein expression with the clinico-pathological features of breast cancer patients.

Smac/DIABLO protein promotes caspase-dependent apoptosis by inhibition of inhibitor of apoptosis protein (IAP) family members. The role of Smac/DIABLO in breast cancer has not been yet established. Therefore, the aim of the study was to assess the expression of this protein in tumor cells from breast cancer patients. The expression of Smac/DIABLO was analyzed in 62 breast cancer patients by flow cytometry. The obtained results were compared with expression of this protein in benign breast tumor tissue, which served as the control (11 patients with fibroadenoma). Expression of caspase-3 proteins in breast cancer was also evaluated. Smac/DIABLO expression in breast cancer was correlated with clinical and pathological data. Although the expression of Smac/DIABLO protein was found in all examined samples of both the breast cancer and fibroadenoma patients, the median expression of Smac/Diablo in breast cancer was significantly lower than in the control (39.1% vs. 48.1%; p=0.0047). Smac/DIABLO expression correlated with expression of caspase-3 (p=0.000008). In pT1 breast cancer patients, expression of Smac/DIABLO protein was higher than in those with pT2-3 (p=0.02). Diffuse cancer infiltration significantly correlated with lower expression of Smac/DIABLO protein (p=0.02). Moreover, there was a loose correlation between low expression of Smac/DIABLO protein and cancer embolus in minor blood and lymphatic vessels (p=0.08). Our results indicate that expression of Smac/DIABLO inversely correlates with the tumor stage, which may suggest that this protein may play an important role in the breast cancer development.

Does fecal diversion offer any chance for spontaneous closure of the radiation-induced rectovaginal fistula?

Analysis of the clinical course of patients with postirradiation rectovaginal fistula after fecal diversion. The studied group included 17 women with postirradiation rectovaginal fistula who underwent fecal diversion as a sole mode of treatment, between January 1987 and December 2002, in our department. All patients were subjected to radiotherapy due to cancer of the uterine cervix, administered 5-107 months before the fistula appearance (mean, 22.9 months). In 3 of 17 patients (18%), spontaneous closure of fistula was observed after 5, 6, and 9 months, respectively, from fecal diversion. Closure was confirmed by endoscopy. Length of follow-up after fecal diversion ranged from 0.5 to 122 months. The actuarial probability of spontaneous closure of postradiotherapy rectovaginal fistula was 0.24 at 9 months of follow-up and then remained stable thereafter. In conclusion, colostomy alone gives hardly a chance for closure of the postradiotherapy rectovaginal fistula. Additional surgical measures are necessary.

Astonishingly rapid growth of malignant cystosarcoma phyllodes tumor in a pregnant woman--a case report.

There are very few reports concerning the presence of malignant cystosarcoma phyllodes (CSP) in breasts of pregnant women. In the hereby described case, a 28-year-old woman presented in our department with huge (18 x 11 x 8 cm) tumor of left breast, 2 weeks after labor. The patient discovered a tumor in 34th week of pregnancy, 6 weeks before labor. Histopatholgic examination of excised tumor revealed the presence of malignant CSP tumor. Simple mastectomy was proposed to patient as a best treatment modality. However, the patient refused. She underwent excision of tumor bed (2-cm tumor-free margin was achieved). Despite insufficient treatment, she remains free of disease 20 months after the wide excision of breast malignancy. It is not known how pregnancy influences prognosis of patients with malignant CSP. Lack of such information prompted us to describe the clinical course of our patient.

Sentinel node biopsy in patients with breast cancer--evaluation of exposure to radiation of medical staff.

AIM: To measure the absorbed doses of radiation to hands of medical staff performing sentinel node biopsy in breast cancer patients. METHODS: The study was conducted in 2004, during sentinel node biopsies in 13 breast cancer patients (T1/T2N0). Sentinel nodes were identified with the use of combined radiotracer/blue dye technique (lymphoscintigraphy--99mTc on albumin carrier, surgery after 24 h; blue dye; intraoperative detection of gamma radiation). Highly sensitive thermoluminescent dosimeters (TLD) made of LiF were used to assess the absorbed doses of radiation during the procedure. During lymphoscintigraphy and during surgical procedure a total of 57 TLDs was placed on different parts of hands of medical staff. RESULTS: Maximal dose recorded during lymphoscintigraphy by TLDs placed on the hands of the physician injecting the radiotracer was 164 microSv. Mean recorded doses were higher for non-dominant hand, especially for distal parts of the index finger, third finger and thumb. During the surgical procedure, TLDs placed on the hands of medical staff recorded much lower doses of radiation than during lymphoscintigraphy. The highest dose was recorded by TLD placed on the pulp of the dominant hand index finger (22 microSv) of the operating surgeon. Mean doses recorded by TLDs placed on the hands of the operating surgeon ranged from 2 to 8 microSv. The absorbed dose of radiation to hands of the scrub nurse was similar to that absorbed to hands of the operating surgeon. CONCLUSION: The maximum recorded dose during sentinel node biopsy in this study was 2200 times smaller than current 1-year dose limit.

Biosynthesis of deuterated riboflavin: structure determination by NMR and mass spectrometry.

The riboflavin-producing fungus Eremothecium ashbyii was cultured in various growth media containing high concentrations of deuteriuj, and the product was isolated. The structures of highly deuterated riboflavin, in which at least 13 of 15 nonexchangeable hydrogens were replaced by deuterium, and fully deuterated riboflavin, in which all 15 nonexchangeable sites contained deuterium, were established by NMR and mass spectrometry. The aromatic protons (C-5 and C-8) wer partially substituted in the highly deuterated molecule. Information regarding three areas of the biosynthetic pathway within the microorganism was obtained as a result of the formation of these compounds. Extensive solvent interaction, possibly due to passage of sugar through the transaldolase-transketolase pathway, occurs during formation of the ribityl chain. Limited solvent participation takes place during formation of 6,7-dimethyl-8-ribityllumazine, the immediate precursor of riboflavin. Deuteration of the riboflavin C-6 and C-7 methyl groups indicates significant solvent exchange during the final step of the biosynthetic process.