がんの科学と治療

Background: Ovarian cancer is the most common cause of death among patients diagnosed with reproductive organ cancers in Poland. Despite the progress and continual improvements in diagnostic techniques and methods of cancer treatment, the epidemiology and natural history of ovarian cancer remain largely unchanged. Approximately three quarters of ovarian carcinoma cases are not detected or treated until the third or fourth stage of the disease. The current routine diagnostic procedures include ultrasound examination, biochemistry marker assessments and histopathological evaluations of ovarian tissue to confirm a diagnosis. The preoperative diagnosis of ovarian cancer remains unsatisfactory, and the search for new effective methods has not provided satisfactory results.
Objectives: To determine whether routine biopsy of macroscopically unchanged ovaries provides sufficient benefit.
Material and methods: We conducted a clinical trial involving approximately 1,000 ovaries from which tissue samples were collected during reproductive organ surgeries, and the tissues were examined by a pathologist. Spearman’s rank correlation was used to compare the results statistically.
Results: The results of the histopathological evaluation of macroscopically unchanged ovaries were normal in 99.8% of patients.
Conclusion: In this context, routine biopsy of macroscopically unchanged ovaries does not provide sufficient benefit. Moreover, it may be associated with increases in surgical complications such as bleeding from the biopsy site. Therefore, biopsy of the ovaries during surgery of reproductive organs should not be performed routinely unless cancer is suspected.

Purpose: To study and assess to the sensitivity of Burkitt’s lymphoma cells harboring differential levels of cell surface CD20 for anti-CD20 monoclonal Antibodies.
Material and methods: Burkitt’s lymphoma cell line ‘Daudi’ was used during present study. Cells were exposed to single dose of γ-radiation (0.5 Gy) and thereafter incubated with rituximab (Rtx) or tositumomab (Tst) (0.5 μg/ ml concentration each). The changes in expression of RelA, Akt and Bax/Bcl-2 ratio was measured to assess sensitivity of cells in term of cell death.
Results: During the present investigation, we found that cells incubated with anti-CD20 mAbs at +20 hrs post radiation exposure showed higher levels of cell death in term of Bax/Bcl-2 ratio. In addition, we also found the significant changes in expression of pro-survival signaling proteins such as RelA and Akt pathways. Moreover, we found that tositumomab is a potent inducer of apoptotic cell death.
Conclusion: These findings suggested that the efficacy of anti-CD20 mAbs depends on the number of CD20 molecules expressed on cell surface and type of antibody used. It may provide new treatment options for selection of anti-CD20 mAbs even in aggressive B-cell lymphoma, which harbors low levels of CD20 or even resistant to current therapies in vivo.

Background: The urachus is an embryonic remnant, which is obliterated in most of the adults. Residual of it persists in 32% of adults and neoplasms, which can arise from this structure, are extremely rare. These are usually diagnosed through incidental findings or for urinary symptoms. Their natural history is characterized by an early metastatization through the peritoneal cavity. Due to their rarity, there are no unanimous consensus for their management and therapy. Radical excision, associated or not with intraperitoneal hypertermic chemotherapy linked to cytoreductive surgery, was suggested over time.
Case report: A black woman came to our attention for a gelatinous secretion from the umbilicus. After a MRIstudy, a parietal neoformation of the urachal remnants was diagnosed. This neoformation revealed a cutaneous fistulization and it was excised surgically. Its pathologic exam described the presence of a cystic mucinous urachal tumor. During the follow-up, a cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) was performed, due to the occurence of free intraperitoneal liquid and multiple nodules on the abdominal parenchimas, After the last surgery, the patient underwent radiological and serological follow up and, after 6 months, there are no evidence of pathological recurrence.
Discussion and conclusion: In the diagnostic pathway, the MRI has a pivotal role for the study of the peritoneal cavity. Surgically, the complete excision is preferred. The role of the conventional chemotherapy is still under debate, however CRS in association with HIPEC, is certainly useful.

Sepin-1, a potent non-competitive inhibitor of separase, inhibits cancer cell growth, but the mechanisms of Sepin-1-mediated growth inhibition are not fully understood. Here we report that Sepin-1 hinders growth of breast cancer cells, cell migration, and wound healing. Inhibition of cell growth induced by Sepin-1 in vitro doesn’t appear to be through apoptosis but rather due to growth inhibition. Following Sepin-1 treatment caspases 3 and 7 are not activated and Poly (ADP-ribose) polymerase (Parp) is not cleaved. The expression of Forkhead box protein M1 (FoxM1), a transcription factor, and its target genes in the cell cycle, including Plk1, Cdk1, Aurora A, and Lamin B1, are reduced in a Sepin-1-dependent manner. Expressions of Raf kinase family members A-Raf, B-Raf, and C-Raf also are inhibited following treatment with Sepin-1. Raf is an intermediator in the Raf-Mek-Erk signaling pathway that phosphorylates FoxM1. Activated FoxM1 can promote its own transcription via a positive feedback loop. Sepin-1-induced downregulation of Raf and FoxM1 may inhibit expression of cell cycle-driving genes, resulting in inhibition of cell growth.

To explore the expression pattern of ERs in NSCLC tissues and assess their relationship with tumor histopathological variable. In our study, Ers expression was examined using Real-time PCR with specimens of 28 NSCLC patients. It was shown that both ERÉ‘ and Erβ were over expression in NSCLC tissues, and also the Mrna concentration of both ERÉ‘ and Erβ were significantly higher in primary tumor T2 stage than in T1 stage and higher in squamous carcinoma than in adenocarcinoma. However, the activation of ERÉ‘ and Erβ were completely different. To further explore the role of Ers in development and progression of NSCLC, we used Ers selective siRNA or antagonist in vitro experiments. The results showed that Erβ but not ERÉ‘ can mediate E2 induced cell growth, since siRNA targeting Erβ but not ERÉ‘ gene can induce cell cycle arrest at G1 phase by down regulation of cyclinD1 expression, and also cell cycle regulators p21Waf1/Cip1 and p53 were involved in this signaling pathway.