Nezih Meydan

NF-KappaB expression correlates with apoptosis and angiogenesis in clear cell renal cell carcinoma tissues

BackgroundClear cell renal cell carcinoma (ccRCC) is the most frequently encountered tumor in the adult kidney. Many factors are known to take part in the development and progression of this tumor. Nuclear factor kappa B (NF-κB) is a family of the genes that includes five members acting in events such as inflammation and apoptosis. In this study, the role of NF-κB (p50 subunit) in ccRCC and its relation to angiogenesis and apoptosis were investigated.MethodsFormalin-fixed and paraffin embedded tissue blocks from 40 patients with ccRCC were studied. Expressions of NF-κB (p50), VEGF, EGFR, bc1-2 and p53 were detected immunohistochemically. The relationship of NF-κB with these markers and clinicopathological findings were evaluated.ResultsThe expression of NF-κB was detected in 35 (85%), VEGF in 37 (92.5%), EGFR in 38 (95%), bc1-2 in 33 (82.5%) and p53 in 13 (32.5%) of 40 ccRCC patients. Statistical analyses revealed a significant relation between NF-κB expression and VEGF (p = 0.001), EGFR (p = 0.004), bc1-2 (p = 0.010) and p53 (p = 0.037). There was no significant correlation between NF-κB and such parameters as tumor grade, stage, age and sex.ConclusionThe results of this study indicated that in ccRCC cases NF-κB was associated with markers of angiogenesis and apoptosis such as VEGF, EGFR, bc1-2 and p53. In addition, the results did not only suggest a close relationship between NF-κB and VEGF, EGFR, bc1-2 and p53 in ccRCC, but also indicate that NF-κB was a potential therapeutic target in the treatment of ccRCC resistant to chemotherapy.

Urinary Stone Disease in Diabetes Mellitus

Objective: Diabetes mellitus (DM) and urinary stone disease (USD) are common diseases in the community. The prevalence of USD has not previously been studied in DM patients. Material and Methods: We evaluated 286 diabetics and 111 age-matched controls by means of direct urinary system X-ray, ultrasonography and/or intravenous pyelography. We also examined the history, risk factors and clinical aspects of USD in DM patients. Results: The prevalence of USD (21% vs 8%; p r < r 0.05) and the rate of recurrence (2.1 r - r 2.2 vs 1.3 r - r 0.5 stones/case; p r < r 0.05) were higher in the diabetics compared to the controls. Family history and male gender were significant risk factors for the development of USD in the DM patients. Increased daily total fluid consumption was not preventive for USD in the DM patients, and the type of fluid consumed did not have an impact on the risk of USD. Alcohol consumption was a significant risk factor for the development USD in the DM patients (odds ratio 3.68; 95% confidence interval 1.29-10.45; p r < r 0.05). Crystaluria (10% vs 1%; p r < r 0.05) and positive urine culture (8% vs 1%; p r < r 0.05) were also more prominent in the diabetics compared to the controls. Conclusions: The results of this study suggest that DM is a risk factor for the development USD.

Biological characteristics of breast cancer at the primary tumour and the involved lymph nodes

Diminished oestrogen receptor (ER) expression in the involved axillary lymph nodes (ALN) in breast cancer compared with the primary tumour has been reported in previous studies. We have assessed a wider spectrum of tumour markers (ER, progesterone receptor (PgR), p53, Ki‐67 and HER‐2/neu) and compared extent and staining intensities at the primary tumour and the involved ALN on specimens of 22 cases with invasive ductal breast cancer. At the involved ALN, both the quantity of positive staining cells and the staining intensities for ER and PgR were decreased (p < 0.001 and p = 0.003, respectively). In contrast, the quantity of positive staining cells (p < 0.004) and the staining intensities for Ki‐67 were increased. The differences for HER‐2/neu and p53 staining at both sites were insignificant. The immunohistochemical staining properties of both the primary tumour and the ALN metastases showed no correlation with the number of involved ALN (p > 0.05). This study suggested that ALN metastasis might indicate a more unfavourable expression pattern of ER, PgR and Ki‐67 in invasive ductal breast cancer.

Cisplatin plus gemcitabine chemotherapy in taxane/anthracycline-resistant metastatic breast cancer.

Background: The most commonly used chemotherapeutic regimens in the treatment of metastatic breast cancer (MBC) include anthracyclines and taxanes. In our study, we investigated the efficacy and tolerability of cisplatin plus gemcitabine combination chemotherapy regimen in patients with MBC, who exhibited disease progression after anthracycline- and taxane-based chemotherapy. Methods: Thirty-three patients with taxane/anthracycline-resistant MBC have been treated with gemcitabine 1,000 mg/m2 intravenously and cisplatin 30 mg/m2 intravenously on days 1 and 8 of a 3-week treatment cycle. Results: Thirty-one patients were assessable for response. One of the 31 patients (3.2%) showed complete response, while 7 patients (22.6%) showed partial response; the objective response rate was 25.8%. Stable and progressive disease was observed in 6 (19.4%) and 17 patients (54.8%), respectively. The median time to progression was 4 months (95% CI 2.15–5.85). The median survival time of all patients was 9.5 months (95% CI 7.86–11.14). Conclusion: Gemcitabine and cisplatin combination therapy is moderately active and safe in patients with MBC previously treated with anthracycline and taxanes.

A new perspective on cardiotoxicity of 5-fluorouracil. A novel research tool 'cardiac ultrasonic integrated backscatter analysis' indicates transient, subclinical myocardial dysfunction due to high-dose leucovorin and infusional 5-fluorouracil regimen.

Background: The pathophysiology of 5-fluorouracil (5-FU) cardiotoxicity is still controversial. The objective of this study was to assess the influence of high-dose leucovorin and infusional 5-FU regimen (HDLV5FU) on cardiac tissues. Methods: We monitored 28 patients (median age 68 years) under HDLV5FU chemotherapy with complete blood counts, cardiac enzymes, C-reactive protein, coagulation tests, Holter electrocardiogram, and conventional echocardiography. Cardiac ultrasonic tissue characterization with integrated backscatter (IBS) analysis was performed in the 16 last enrolled patients. Results: The magnitude of both anterior and posterior cardiac IBS values significantly decreased at the 48th hour of treatment compared to both 0th hour and day 15 (p < 0.003). Cardiac IBS values on the 15th day were not different from the 0th hour. Clinical cardiotoxicity was not observed and other monitored parameters did not change significantly in any patient (p > 0.5 for all). Conclusion: Cardiac IBS analysis suggests that 5-FU might cause reversible subclinical myocardial dysfunction.

Id-1: Regulator of EGFR and VEGF and potential target for colorectal cancer therapy

BackgroundThe helix-loop-helix transcription factor Id-1 (an inhibitor of differentiation and DNA binding) plays a role in development and progression of many tumours. Id-1 is known to exert its effects on the epidermal growth factor receptor (EGFR) and the vascular endothelial growth factor (VEGF). The aim of this study was to reveal whether there was a relationship between Id-1 and EGFR and VEGF in colorectal carcinoma.MethodsTumour and non-tumour tissue specimens from 46 cases of colorectal carcinoma were exposed to immunohistochemical staining for Id-1, EGFR and VEGF. The relationship between the degree of staining and tumour grade, tumour stage and all tumour markers was investigated.ResultsTumour cells showed positive staining for Id-1 in 43 cases (93.5%), for EGFR in 41 cases (89%) and for VEGF in 42 cases (91%). There was a significant relation between the tumour grade and the degree of staining for Id-1, EGFR and VEGF. The relation between the tumour stage and the degree of staining for Id-1, EGFR and VEGF was also significant. There was a significant relation between Id-1 expression and EGFR and VEGF expressions. Non-tumoural tissue specimens were not stained with Id-1 and EGFR antibodies in any of the cases, but stained with VEGF antibody in 3 cases.ConclusionThis study revealed that Id-1, EGFR and VEGF took part in development and progression of colorectal carcinomas and that Id-1 was associated with regulations of EGFR and VEGF. The results of this study support the idea that not only EGFR and VEGF but also Id-1 could be new targets in cancer treatment.

Extravasation of paclitaxel into breast tissue from central catheter port.

Abstract. A 53-year-old woman with advanced-stage ovarian cancer experienced extravasation of paclitaxel into the breast tissue as a result of inappropriate needle insertion and/or dislodgement; it came from a central catheter port (CCP) that was found to be intact under radiological examination with contrast material. The breast became tender and oedematous with erythema, and local warming was observed within a few hours. The patient improved in the next few days during nonsteroidal anti-inflammatory medication and close observation, and the breast healed with thickened and darkened skin and central scarring in the 6th month of follow-up. To the best of our knowledge, extravasation into breast tissue is rare in the literature. Extravasation of vesicant drugs from CCP can cause tissue necrosis; it is therefore essential that ports be carefully assessed and used by experienced staff to lessen the likelihood of such an unpleasant complication.

Influence of high-dose leucovorin and 5-fluorouracil chemotherapy regimen on P wave duration and dispersion

Background:  Although 5‐fluorouracil (5‐FU)‐related cardiotoxicity is well known, atrial arrhythmia, as a potentially serious complication has not been studied in detail. The aim of this study was to determine the P max and Pd in the electrocardiograms (ECG) of patients receiving 5‐FU treatment.

Paclitaxel-carboplatin induced radiation recall colitis.

Some chemotherapeutic agents can “recall” the irradiated volumes by skin or pulmonary reactions in cancer patients who previously received radiation therapy. We report a recall colitis following the administration of paclitaxel-containing regimen in a patient who had been irradiated for a carcinoma of the uterine cervix. A 63-year-old woman underwent a Wertheim operation because of uterine cervix carcinoma. After 8 years of follow-up, a local recurrence was observed and she received curative external radiotherapy (45 Gy) to the pelvis. No significant adverse events were observed during the radiotherapy. Approximately one year later, she was hospitalized because of metastatic disease with multiple pulmonary nodules, and a chemotherapy regimen consisting of paclitaxel and carboplatin was administered. The day after the administration of chemotherapy the patient had diarrhea and rectal bleeding. Histological examination of the biopsy taken from rectal hyperemic lesions showed a radiation colitis. The symptoms reappeared after the administration of each course of chemotherapy and continued until the death of the patient despite the interruption of the chemotherapy. In conclusion, the probability of recall phenomena should be kept in mind in patients who received previously with pelvic radiotherapy and treated later with cytotoxic chemotherapy.

Anti-Yo Antibody-mediated Paraneoplastic Cerebellar Degeneration in a Female Patient with Pleural Malignant Mesothelioma

Paraneoplastic cerebellar degeneration is a rare non-metastatic complication of malignancies. It presents with acute or subacute onset of ataxia, dysarthria and intention tremor. Paraneoplastic cerebellar degeneration is most commonly associated with malignancies of the ovary, breast and lung. The anti-Yo (anti-Purkinje cells) antibodies that specifically damage the Purkinje cells of the cerebellum are found in the serum and cerebrospinal fluid. Anti-Yo-related paraneoplastic cerebellar degeneration is most commonly found in women with gynecological and breast cancers, but it is reported in other malignancies. Patients with paraneoplastic syndromes most often present with neurologic symptoms before an underlying cancer is detected. We report a case of anti-Yo-related paraneoplastic cerebellar degeneration associated with pleural malignant mesothelioma in a 51-year-old female patient. She presented to our department with a 2-week history after the last chemotherapy of progressive dizziness related to head movement, nausea, vomiting, ataxia and unsteady gait. A western blot assay was negative for anti-Hu, anti-Ri, anti-Ma2, anti-CV2 and anti-amphiphysin paraneoplastic antibody markers but positive for anti-Yo. In conclusion, we report a case of paraneoplastic cerebellar degeneration in a patient with pleural malignant mesothelioma because of the rarity of this neurologic presentation after the diagnosis of malignant mesothelioma and of the association with anti-Yo antibodies.