Alina Morawiec-Bajda

Role of impaired DNA repair in genotoxic susceptibility of patients with head and neck cancer.

DNA repair is critical for genotoxic susceptibility and cancer development. Forty-seven patients with head and neck squamous cell carcinoma (HNSCC) and 38 healthy controls were enrolled in this study. Among the patients, 16 subjects had metastasis of HNSCC. The extent of DNA damage, including oxidative lesions, and efficiency of repair after genotoxic treatment with hydrogen peroxide were examined using the alkaline comet assay. HNSCC cells were sensitive to genotoxic treatment and displayed impaired DNA repair. In particular, lesions caused by hydrogen peroxide were repaired less effectively in cancer cells from patients with metastasis than in cells from healthy controls. We suggest that impaired DNA repair might play a role in genotoxic susceptibility of patients with head and neck cancer. Finally, as a consequence of this finding we have shown that treatment with DNA-reactive drugs could be considered as an effective therapy strategy for head and neck cancer.

Comparative study of DNA damage and repair in head and neck cancer after radiation treatment.

We compared DNA damage and the efficacy of its repair after genotoxic treatment with γ‐radiation of lymphocytes and tissue cells isolated from patients with squamous cell carcinoma of head and neck (HNSCC) and healthy donors. Thirty‐seven subjects with HNSCC and 35 healthy donors were enrolled in the study. The extent of DNA damage including oxidative lesions and efficiency of the repair were examined by alkaline comet assay. HNSCC cancer cells were more sensitive to genotoxic treatment and displayed impaired DNA repair. In particular, lesions caused by γ‐radiation were repaired less effectively in metastasis of HNSCC than in healthy controls. The differences in radiation sensitivity of cancer and control cells suggested that DNA repair might be critical for HNSCC treatment. We conclude that γ‐radiation might be considered as an effective therapeutic strategy for head and neck cancers, including patients in advanced stage of the disease with clear evidence of metastasis.

Imatinib (STI571) Inhibits DNA Repair in Human Leukemia Oncogenic Tyrosine Kinase-Expressing Cells

Abstract BCR/ABL oncogene, as a result of chromosome aberration t(9;22), is the pathogenic principle of almost 95% of human chronic myeloid leukemia (CML). Imatinib (STI571) is a highly selective inhibitor of BCR/ABL oncogenic tyrosine kinase used in leukemia treatment. It has been suggested that BCR/ABL may contribute to the resistance of leukemic cells to drug and radiation through stimulation of DNA repair in these cells. To evaluate further the influence of STI571 on DNA repair we studied the efficacy of this process in BCR/ABLpositive and -negative cells using single cell electrophoresis (comet assay). In our experiments, K562 human chronic myeloid leukemia cells expressing BCR/ABL and CCRF-CEM human acute lymphoblastic leukemia cells without BCR/ABL expression were employed. The cells were exposed for 1 h at 37 ∞C to N-methyl-N’-nitro-N-nitrosoguanidine (MNNG) at 5 μᴍ, mitomycin C (MMC) at 50 μᴍ or to γ-radiation at 15 Gy with or without a 24 h preincubation at 1 μᴍ of STI571. The MTT cells survival after 4 days of culture showed that STI571 enhanced the cytotoxity of the examined compounds in the K562 line. Further it was found, that the inhibitor decreased the efficacy of DNA repair challenged by each agent, but only in the K562 expressing BCR/ABL. Due to the variety of DNA damage induced by the employed agents in this study we can speculate, that BCR/ABL may stimulate multiple pathways of DNA repair. These results extend our previous studies performed on BCR/ABLtransformed mouse cells onto human cells. It is shown that BCR/ABL stimulated DNA repair in human leukemia cells. In conclusion we report that STI571 was found to inhibit DNA repair and abrogate BCR/ABL-positive human leukemia cells therapeutic resistance.

Helicobacter pylori infection can modulate the susceptibility of gastric mucosa cells to MNNG

The pathogenesis of stomach cells can be associated with their susceptibility to exogenous dietary irritants, like nitrosamines such as dimethylnitrosamines (DMNA), and to the effects of non-dietary factors, including Helicobacter pylori infection. We used N-methyl-N’-nitro N-nitrosoguanidyne (MNNG) as a surrogate agent that induces a spectrum of DNA damage similar to DMNA. Using the alkaline comet assay, we showed that antioxidants — vitamins C and E, quercetin, and melatonin — reduced the genotoxic effect of MNNG in H. pylori-infected and non-infected human gastric mucosa cells (GMCs). To compare the sensitivity of the stomach and the blood, the experiment was also carried out in peripheral blood. We observed a higher level of DNA damage induced by MNNG in H. pylori-infected than in noninfected GMCs. We did not note any difference in the efficacy of the repair of the damage in either type of GMC. H. pylori infection may play an important role in the pathogenesis of GMCs, as it can modulate their susceptibility to dietary mutagens/carcinogens, thus contributing to gastric cancer.

Izolowana sarkoidoza szyi – opis dwóch przypadków ☆ ☆☆ ★

Summary Although the first description of sarcoidosis comes from 1877, its etiology still has not been determined. Its frequency in Europe is estimated at 10–80 new cases per 100 thousand people. Sarcoidosis is a granulomatous disease, manifesting mostly in enlargement of lymph nodes of a pulmonary hilus, in changes in pulmonary parenchyma and skin, eyeball, spleen and liver. Changes in about 30% cases also occur in lymph nodes of other regions (neck or retroperitoneal lymph nodes). Changes in salivary glands and heart have also been reported. Isolated sarcoidosis of peripheral lymph nodes occurs rarely. The paper presents two cases of the isolated sarcoidosis of neck lymph nodes. One of them relates to a 70-year-old woman, in which a lymph node sarcoidosis preceded by several months the occurrence of a typical systemic sarcoidosis engaging pulmonary hiluses. The other case is a 30-year-old man, in which the isolated sarcoidosis of lymph nodes was originally diagnosed as a tumor of a submandibular salivary gland. The difficulties in diagnostics of the isolated neck sarcoidosis is discussed as well as its atypical course in both described cases.Although the first description of sarcoidosis comes from 1877, its etiology still has not been determined. Its frequency in Europe is estimated at 10-80 new cases per 100 thousand people. Sarcoidosis is a granulomatous disease, manifesting mostly in enlargement of lymph nodes of a pulmonary hilus, in changes in pulmonary parenchyma and skin, eyeball, spleen and liver. Changes in about 30% cases also occur in lymph nodes of other regions (neck or retroperitoneal lymph nodes). Changes in salivary glands and heart have also been reported. Isolated sarcoidosis of peripheral lymph nodes occurs rarely. The paper presents two cases of the isolated sarcoidosis of neck lymph nodes. One of them relates to a 70-year-old woman, in which a lymph node sarcoidosis preceded by several months the occurrence of a typical systemic sarcoidosis engaging pulmonary hiluses. The other case is a 30-year-old man, in which the isolated sarcoidosis of lymph nodes was originally diagnosed as a tumor of a submandibular salivary gland. The difficulties in diagnostics of the isolated neck sarcoidosis is discussed as well as its atypical course in both described cases.

Trudności diagnostyczne w przypadku raka zachyłka gruszkowatego u mężczyzny

Despite a use of many diagnostic tools to assess the stage of the carcinoma of hypopharynx and larynx various problems can still arise. A 45 years old man was admitted with an initial diagnosis of carcinoma of the hypopharynx with metastases to neck lymphnodes (Tin situ N1). Computed tomography of the neck revealed pathologic remodeling of the thyroid cartilage. An oncologist decided to commence a chemotherapy. After 4 cycles of chemotherapy a second CT scan revealed a suspected neoplastic infiltration of the cricoid and thyroid cartilages. After that the patients was disqualified from both radio- and chemotherapy. The consulting laryngologist did not find any pathologies in the larynx and hypopharynx. On palpation there were no enlarged neck lymph nodes. The second specimen taken from the right pyriform sinus was a loosen fragment of the epithelium with the Ca male differentiatum G3. The positron emission tomography imaging found a suspected site 11 mm in diameter situated in front of the carotid vessels. The neoplastic infiltration of the larynx was not confirmed. The patient started the radiotherapy. We are of the opinion that in the presented case the erroneous interpretation of the CT scan was a likely consequence of the improper setting of a window of brightness and contrast. Strong artifacts are also observed in 3D imaging. Another cause of the diagnostic problems could stem form an unfinished calcification of the cartilages which produced an image of irregular areas of calcification and rarely diagnosed T in situ in a pyriform sinus.Summary Despite a use of many diagnostic tools to assess the stage of the carcinoma of hypopharynx and larynx various problems can still arise. A 45 years old man was admitted with an initial diagnosis of carcinoma of the hypopharynx with metastases to neck lymphnodes (Tin situ N1). Computed tomography of the neck revealed pathologic remodeling of the thyroid cartilage. An oncologist decided to commence a chemotherapy. After 4 cycles of chemotherapy a second CT scan revealed a suspected neoplastic infiltration of the cricoid and thyroid cartilages. After that the patients was disqualified from both radio- and chemotherapy. The consulting laryngologist did not find any pathologies in the larynx and hypopharynx. On palpation there were no enlarged neck lymph nodes. The second specimen taken from the right pyriform sinus was a loosen fragment of the epithelium with the Ca male differentiatum G3. The positron emission tomography imaging found a suspected site 11 mm in diameter situated in front of the carotid vessels. The neoplastic infiltration of the larynx was not confirmed. The patient started the radiotherapy. We are of the opinion that in the presented case the erroneous interpretation of the CT scan was a likely consequence of the improper setting of a window of brightness and contrast. Strong artifacts are also observed in 3D imaging. Another cause of the diagnostic problems could stem form an unfinished calcification of the cartilages which produced an image of irregular areas of calcification and rarely diagnosed T in situ in a pyriform sinus.

Szkliwiak zatoki szczękowej – opis przypadku☆

Ameloblastoma (adamantinoma) is a benign neoplasm deriving from the enamel organ. Its etiology has not been ultimately determined. It constitutes about 1% of all head and neck tumours, and about 11% of teeth-originating tumours. Usually it occurs in the mandible near premolar and molar teeth, more rarely in its anterior part. About 20% of described cases of ameloblastoma relate to the jaw, its very rare location is gingiva or cheak tunica mucosa. The essay presents a case of ameloblastoma of a maxillary sinus in a 65-year-old man. The diagnostic and treatment algorithm in ameloblastoma is discussed.Summary Ameloblastoma (adamantinoma) is a benign neoplasm deriving from the enamel organ. Its etiology has not been ultimately determined. It constitutes about 1% of all head and neck tumours, and about 11% of teeth-originating tumours. Usually it occurs in the mandible near premolar and molar teeth, more rarely in its anterior part. About 20% of described cases of ameloblastoma relate to the jaw, its very rare location is gingiva or cheak tunica mucosa. The essay presents a case of ameloblastoma of a maxillary sinus in a 65-year-old man. The diagnostic and treatment algorithm in ameloblastoma is discussed.

Diagnosing head and neck cancer using the photodynamic method

Authors described one of diagnostic method in oncology Photodynamic Therapy (PDT) to recognizing head and neck cancer. They used own, modified way to inserting the photosensitizer in cancer cells. The aim of this report was presentation some patients who were suspected cancer disease of laryngeal organs on based of PDT and biopsy. The comparison of these results confirmed efficacy of PDT as diagnostic method.