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Downregulation of ING3 mRNA expression predicts poor prognosis in head and neck cancer

Although many clinical and pathological prognostic factors such as tumor stage and lymph‐node involvement have been described, to date no reliable or clinically applicable marker or tumor aggressiveness has been identified for head and neck cancer. In an attempt to identify such a molecular prognostic marker, we analyzed the mRNA expression status of ING3 by quantitative reverse transcription–polymerase chain reaction. We also examined p53 mutation status and investigated its relationship with ING3, as well its clinicopathological characteristics. About half of the 71 tumor samples demonstrated downregulation of ING3 compared to their matched normal counterparts. Although most clinicopathological variables were not significantly related to ING3 downregulation or p53 mutation status, a significant relationship was detected in terms of overall survival between the cases with low and normal to high ING3 expression. At 5 years follow up, approximately 60% of the patients with normal to high ING3 expression survived, whereas this was 35% in the patients with low ING3 expression. Multivariate analysis also showed downregulation of ING3 as an independent prognostic factor for poor overall survival. These results reveal that ING3 would function as a potential tumor suppressor molecule and that low levels of ING3 may indicate an aggressive nature of head and neck cancer. (Cancer Sci 2008; 99: 531–538)

Protection against cisplatin-induced nephrotoxicity by recombinant human erythropoietin.

Cisplatin (CDDP) is a potent nephrotoxin, and nephrotoxicity is its most important dose-limiting toxicity. In this study, we aimed to investigate the role of recombinant human erythropoietin (rhEPO) in the protection of cisplatin-induced nephrotoxicity and compare its efficacy with the cell-protective agent amifostine. All experiments were conducted on female Wistar albino rats. Animals were randomly assigned to four groups, each including six rats. Group A received only CDDP, group B received CDDP plus rhEPO, group C received CDDP plus amifostine, and group D received only rhEPO. At the end of 7 wk, hemoglobin (Hgb), hematocrite (Htc), blood urea nitrogen (BUN), and creatinine (Cr) levels were determined and kidneys of the rats were removed. The weights of the kidneys were measured and sent for histopathological examination. Proximal tubules from four areas of the kidney (outer cortex, inner cortex, the medullary ray, and outer stripe of outer medulla [OSOM]) were evaluated. There were statistically significant differences among the groups in terms of tubular scores, including overall renal tubular score, cortex, inner cortex, OSOM, and medullary ray tubular scores, and Htc levels. Group A rats had the worse tubular scores in all categories when compared to group D rats. When the results of groups B and C were compared, there were no differences in terms of BUN, Cr levels, and tubular scores, but the Htc level was significantly higher in group B. Group B rats had better overall and OSOM tubular scores when compared to group A. Group C also had better overall and OSOM tubular scores compared to group A. The present study showed for the first time that rhEPO plays an important role in the prevention of cisplatin-induced nephrotoxicity and it is as effective as amifostine.

Protective effect of amifostine against cisplatin-induced motor neuropathy in rat.

Cisplatin (CDDP) is a potent anticancer drug. Neurotoxicity is one of the most important dose-limiting toxicity of CDDP. We investigated the role of amifostine in the protection against CDDP-induced neurotoxicity especially on the motor nerves. All experiments were conducted on female Wistar albino rats. Animals were randomly assigned to two groups, each including six rats. Group A received CDDP plus amifostine and Group B received CDDP only. Electroneurography (ENG) was carried out in the beginning and at the end of 7 wk; then, the rats were sacrificed and the sciatic nerve was removed for histopathological examination.The mean initial latency was 2.4667 msn for group A and 2.44833 msn for group B. After 7 wk of treatment, the latency was 2.9167 for group A and 2.6333 for group B. The difference in latencies was not statistically significant. The amplitude was 11.7853 mV and 13.533 mV for groups A and B, respectively. After 7 wk of treatment, the amplitude was 9.400 mV and 9.000 mV, respectively. The decrease of amplitude in compound muscle action potential (CMAP) was 20% in the amifostine group and the decrease was 33% in the untreated group. The mean area of the CMAP in group A was 9.400 mVsn initially and 9.666 mVsn at the end of the treatment; there was a 0.3% increase despite CDDP treatment. In group B, the mean area of the CMAP was 13.816 mVsn initially and 11.857 mVsn at the end of the treatment; this corresponded to a statistically significant 14% decrease as a result of CDDP treatment. The ENG and histopathological studies showed that at the given dose and schedule CDDP-induced motor neuropathy and amifostine reduced this neuropathy both by protection of the amplitude and area of the CMAP in ENG studies and by sparing a larger number of nerve fibers.

PREVENTION OF RADIATION-INDUCED RETINOPATHY WITH AMIFOSTINE IN WISTAR ALBINO RATS.

Purpose: To evaluate the radioprotective efficacy of amifostine on irradiated mature rat retina. Methods: A total of 108 Wistar albino rats were categorized into 3 groups, namely, apoptosis (n = 48), acute effects (n = 40), and late changes in retinal cell layers (n = 20). Each group was further subcategorized into 4 arms: control, amifostine (A), radiotherapy + placebo (RT), and RT + A arms, respectively. Intraperitoneal amifostine (260 mg/kg) was administrated to A and RT + A arms 30 minutes before irradiation. Control and A groups were sham-irradiated, whereas a single dose of 20 Gy whole-cranium irradiation was delivered to RT and RT + A arms. Apoptosis was assessed in 8, 12, and 18 hours after irradiation. Electron microscope was used 2 weeks after irradiation for evaluation and scoring of early morphologic changes in retina. Late effects were assessed and scored accordingly by using both the electron and the light microscope on Week 10. Results: At acute phase, although no notable change was seen in 8 hours, significant increase in apoptosis was detected in 12 hours in RT arm (P = 0.029). Comparative analyses between the groups in 3 different time points displayed a higher apoptotic rate in RT group than the RT + A group (P = 0.008). Similarly, comparisons between groups for late effects on the basis of electron microscopic findings revealed lower scores in the RT + A than the RT arm (P < 0.001). Conclusion: This study suggested a potential radioprotective role for amifostine on mature rat retina by reducing radiation-induced apoptosis in retinal cells. These results form a basis for such preclinical investigations and call for future clinical studies.

Pneumocystis carinii pneumonia in an infant with hypogammaglobulinemia

A 4-month-old boy without significant medical history presented with fever, labored breathing and desaturation. Chest radiograph (CXR) revealed bilateral ground-glass opacities with air bronchograms (Fig. 1). High-resolution CT (HRCT) showed diffuse, bilateral, ground-glass airspace opacities with interlobar septal thickening (Fig. 2). The patient was later diagnosed with hypogammaglobulinemia caused by CD40 ligand deficiency and Pneumocystis carinii

Squamous cell carcinoma arising in a sacrococcygeal tailgut cyst

We report a case of squamous cell carcinoma originated from a sacrococcygeal tailgut cyst in a 73-year-old female patient. Tailgut cysts are generally multilocal and have a layer of either columnar, squamous or transitional epithelium, or a combination of these. This case was treated with surgical excision and radiotherapy. Cancer presentation of a congenital abnormality in old age is a rare entity. This report is the first case of squamous cell carcinoma developing in a tailgut cyst without any synchronization, as an isolated (pure) pathology.We report a case of squamous cell carcinoma originated from a sacrococcygeal tailgut cyst in a 73-year-old female patient. Tailgut cysts are generally multilocal and have a layer of either columnar, squamous or transitional epithelium, or a combination of these. This case was treated with surgical excision and radiotherapy. Cancer presentation of a congenital abnormality in old age is a rare entity. This report is the first case of squamous cell carcinoma developing in a tailgut cyst without any synchronization, as an isolated (pure) pathology.

Intensity-Modulated Radiation Therapy Improves the Target Coverage Over 3-D Planning While Meeting Lung Tolerance Doses for All Patients With Malignant Pleural Mesothelioma

Purpose: To investigate high conformality on target coverage and the ability on creating strict lung dose limitation of intensity-modulated radiation therapy in malignant pleural mesothelioma. Patients and Methods: Twenty-four radiation therapy plannings were evaluated and compared with dosimetric outcomes of conformal radiation therapy and intensity-modulated radiation therapy. Hemithoracal radiation therapy was performed on 12 patients with a fraction of 1.8 Gy to a total dose of 50.4 Gy. All organs at risk were contoured. Radiotherapy plannings were differed according to the technique; conformal radiation therapy was planned with conventionally combined photon–electron fields, and intensity-modulated radiation therapy was planned with 7 to 9 radiation beam angles optimized in inverse planning. Strict dose–volume constraints were applied. Results: Intensity-modulated radiation therapy was statistically superior in target coverage and dose homogeneity (intensity-modulated radiation therapy-planning target volume 95 mean 100%; 3-dimensional conformal radiation therapy-planning target volume 95 mean 71.29%, P = .0001; intensity-modulated radiation therapy-planning target volume 105 mean 11.14%; 3-dimensional conformal radiation therapy-planning target volume 105 mean 35.69%, P = .001). The dosimetric results of the remaining lung was below the limitations on intensity-modulated radiation therapy planning data (intensity-modulated radiation therapy-lung mean dose mean 7.5 [range: 5.6%-8.5%]; intensity-modulated radiation therapy-lung V5 mean 55.55% [range: 47%-59.9%]; intensity-modulated radiation therapy-lung V20 mean 4.5% [range: 0.5%-9.5%]; intensity-modulated radiation therapy-lung V13 mean 13.43% [range: 4.2%-22.9%]). Conclusion: With a complex and large target volume of malignant pleural mesothelioma, intensity-modulated radiation therapy has the ability to deliver efficient tumoricidal radiation dose within the safe dose limits of the remaining lung tissue.

Role of triamcinolone in radiation enteritis management.

AIM To investigate the role of triamcinolone in the management of acute and chronic enteritis caused by pelvic radiotherapy. METHODS Twenty-eight patients with rectum adenocarcinoma or endometrium adenocarcinoma were studied. We compared the results of 14 patients treated with injected triamcinolone acetonide (TA) with those of 14 patients who were not treated with TA. For the TA group, 40 mg of TA was injected intramuscularly on the 1(st), 11(th) and 21(st) d of radiotherapy; the control group received no injections. All of the study participants had a median age of 65 years, had undergone postoperative radiotherapy and were evaluated weekly using Radiation Therapy Oncology Group and the European Organization for Research and Treatment of Cancer Acute Morbidity Score Criteria, and complete blood counts for every 10 d. RESULTS Triamcinolone was found to effectively prevent and treat radiation-induced acute gastrointestinal (enteritis) and genitourinary (cystitis) side effects (P = 0.022 and P = 0.023). For the lower GI side effect follow up, 11 patients in the control group had Grade 2 toxicity and 3 patients had Grade 1 toxicity. In the TA group, 5 patients had Grade 2 toxicity and 9 patients had Grade 1 toxicity. For the genitourinary system side effect follow up, 4 patients had Grade 2 toxicity and 6 patients had Grade 1 toxicity. Additionally, 2 patients had Grade 2 toxicity and 2 patients had Grade 1 toxicity. The neutrophil counts did not differ between the TA group and the control group. There was no meaningful difference between age groups and primary cancers. At the 12th mo of follow up, there were no differences between groups for chronic side effects. CONCLUSION Triamcinolone is a moderately potent steroid, that is inexpensive and has a good safety profile. It would be beneficial for reducing medical expenses related to treatment of radiation induced enteritis.