Merging Experimental Design and Nanotechnology for the Development of Optimized Simvastatin Spanlastics: A Promising Combined Strategy for Augmenting the Suppression of Various Human Cancer Cells.

Simvastatin (SMV) is an antihyperlipidemic agent that has been investigated as a possible anti-cancer agent. An obstacle to malignant tumor therapy using drugs is the delivery of adequate levels to the cancer cells while minimizing side effects following their systemic administration. To circumvent this challenge, the researchers directed towards the field of nanotechnology to benefit from the nano-size of the formulation in passively targeting the tumor cells. Thus, our study aimed at investigating the potential of a combined mixture-process variable design for optimization of SMV spanlastics (SMV-SPNs) with minimized particle size and maximized zeta potential to enhance the anticancer activity of the drug. The study investigated the effects of Span® 20 and Tween® 80 as mixture components and sonication time as a process variable on particle size, polydispersity index, and zeta potential as responses. SPNs were prepared using an ethanol injection method. Combining the predicted optimized variables' levels is supposed to achieve the set goals with a desirability of 0.821. The optimized spanlastics exhibited a measured globule size of 128.50 nm, PDI of 0.329, and ZP of -29.11 mV. The percentage relative error between predicted responses and the observed ones were less than 5% for the three responses, indicating the optimization technique credibility. A significant improvement in the cytotoxicity of the optimized formulation against three different cancerous cell lines was observed in comparison with SMV. The inhibitory concentration (IC50) values of MCF-7, HCT-116, and HEPG2 were found to be 0.89, 0.39, and 0.06 µM at 24 h incubation. The enhanced cytotoxicity could be assigned to the possible improved permeation and preferential build-up within the cancerous cells by virtue of the minimized size. These findings imply that SMV-SPNs could be an ideal strategy to combat cancer.

The diagnostic, predictive, and prognostic role of serum epithelial cell adhesion molecule (EpCAM) and vascular cell adhesion molecule-1 (VCAM-1) levels in breast cancer.

The purpose of this study was to determine the clinical significance of vascular cell adhesion molecule-1 (VCAM-1) and epithelial cell adhesion molecule (EpCAM) in breast cancer (BC) patients. Ninety-six BC patients and 30 age- and sex-matched healthy controls were enrolled into this study. Pretreatment serum markers were determined by the solid-phase sandwich (enzyme-linked immunosorbent assay (ELISA)). The median age at diagnosis was 48 years (range 29-80 years). Majority of the patients (71 %) had luminal subtype, and 38.5 % had metastatic disease. Twenty-nine (30 %) patients showed tumor progression, and 20 (21 %) patients died during follow-up. Median progression-free survival (PFS) and overall survival (OS) were 8.6 ± 1.7 and 35.5 ± 1.5 months, respectively. The baseline serum EpCAM levels of the patients were significantly higher than those of the controls (p < 0.001). There was no significant difference in the serum levels of VCAM-1 between the patients and controls (p = 0.47). No significant correlation was detected between the levels of the serum markers and other clinical parameters (p > 0.05). Patients with HER-2-positive and triple-negative tumors had significantly poorer PFS (p = 0.04 and p = 0.001, respectively), while metastatic disease and chemotherapy unresponsiveness had significantly adverse effect on OS analysis (p < 0.001 and p < 0.001, respectively). Neither serum VCAM-1 levels nor serum EpCAM levels were identified to have a prognostic role on either PFS or OS (VCAM-1 p = 0.76 and p = 0.32; EpCAM p = 0.16 and p = 0.69, respectively). Even though any predictive or prognostic role could not be determined for both markers, serum levels of EpCAM were found to have diagnostic value in BC patients.

Spontaneous pneumothorax in children with osteosarcoma: report of three cases and review of the literature.

Spontaneous pneumothorax is a rare manifestation of primary lung cancer or metastasis. It is estimated that < 1% of all cases of spontaneous pneumothorax are tumor-associated and metastatic osteogenic or soft-tissue sarcomas are associated most commonly with pneumothorax especially in the setting of cytotoxic chemotherapy or radiotherapy. In this article, we report three pediatric cases with osteosarcoma that developed spontaneous pneumothorax during chemotherapy with a review of the literature. Two of them had lung metastasis at the time of the detection of pneumothorax and the remaining patient was found to have a bronchopleural fistula. SPx is an emergency situation and early diagnosis and management can improve prognosis and quality of life of the patient however the optimal management has yet to be determined.

Leiomyoma of the seminal vesicle mimicking tumoral extension of prostatic carcinoma.

Leiomyoma of the seminal vesicle is an extremely rare tumour. The diagnosis of this entity is important when it co-exists with prostatic carcinoma, since it can simulate tumour extension from prostate or bladder cancer on MR imaging and lead to overstaging. In this report, we describe a 74-year-old man with a leiomyoma of the seminal vesicle that mimics tumour extension from co-existent prostatic cancer on T2-weighted MR imaging. To our knowledge, this is the first description of imaging findings of concurrent leiomyoma of the seminal vesicle and prostatic carcinoma.

The efficiency of different chemoradiotherapy regimens in patients with paediatric nasopharynx cancer: review of 46 cases.

The purpose of this study was to evaluate the role of combined modality treatment in patients with paediatric nasopharynx cancer (NPC). Forty-six patients with paediatric NPC were retrospectively analysed. Forty-four of 46 patients received combined modality treatment. Five-year overall survival and progression-free survivals were 70% and 72% for the whole group, and only three of 46 patients had loco-regional relapse. Complete remission was obtained in 18 of 45 patients (40%), and the overall survival (94% vs. 62% and 19%, p = 0.0009) and disease-free survivals (93% vs. 70% and 16%, p = 0.0002) were significantly better in complete responders when compared with the patients who had partial response or stable disease. The 5-year overall survival and disease-free survivals of the patients who received neoadjuvant chemotherapy (CT) and radiotherapy (RT) followed by CT were superior to the other groups (77% and 80%, respectively). The number of total CT cycles (p = 0.0001), nodal stage (p = 0.05) and treatment response (p = 0.0009) were significant prognostic factors for overall survival. The treatment type (p = 0.02), the number of total CT cycles (p = 0.0006), nodal stage (p = 0.05) and treatment response (p = 0.0002) were found as significant prognostic factors for disease-free survival. The survival of patients receiving six or more CT cycles was also significantly better than that of patients receiving less than six cycles (p = 0.0001). In patients with locally advanced paediatric NPC, CT should be added to RT to improve outcome. However, a standard protocol is yet to be identified, and further studies evaluating the addition of interferon or immunotherapy to CT and RT shall be performed.

The role of postoperative radiotherapy in node negative breast cancer patients with pT3-T4 disease.

AIMS: To evaluate the role of postmastectomy radiotherapy (PMRT) in patients with pT3-T4N0M0 breast cancer. METHODS: 156 patients with T3-T4N0M0 breast cancer were retrospectively analyzed. RESULTS: Locoregional recurrences were seen in 17 of 156 patients with a median time for development of 27 months (5.7-248.7 months). Two of 9 patients who were not treated with post-operative radiation therapy had locoregional recurrence as compared with 16 of 147 patients receiving radiotherapy. In multivariate analysis, presence of locoregional recurrence was the only significant prognostic factor for overall survival (18% vs. 86%, p<0.001, RR=9.05). The patients with a median number of dissected lymph nodes >or=10 had a significantly better locoregional disease free survival rate as compared with patients with dissected lymph nodes <10 (90% vs. 78%, p=0.04). Chest wall recurrences were clearly higher in patients without chest wall RT since 5 of 49 patients without RT had recurrences in the chest wall region while only 4 of 107 who received chest wall RT had recurrence. However receiving RT to peripherical lymphatic regions had no additional effect on reducing recurrences in these regions (5% vs. 4%). CONCLUSIONS: Due to the lack of phase III randomized trials directly addressing the role of postmastectomy radiotherapy in these stages, our series suggest that postmastectomy radiotherapy to the ipsilateral chest wall is recommended for patients with PT3N0 and T4N0 breast cancer. The need for irradiating axillary or supraclavicular region shall be neglected in patients who undergo sufficient axillary sampling.

Is early postradiation dysplasia almost associated with poor prognosis? A case report and review of the literature.

Following radiotherapy for cervical carcinoma, abnormal cytologic changes have been reported in a number of publications. These reactions occur at varying periods of time following irradiation and do not necessarily reflect the presence of invasive cancer. On the basis of cytologic and histopathologic features, these reactions were determined as postradiation dysplasia (PRD). PRD has been reported to occur in 18.7-26% of patients treated by radiotherapy for cervical cancer. In the literature, it was reported that patients diagnosed with PRD less than 3 years after the initial diagnosis of cervical cancer had a mean survival rate of 33.8% as compared with a 100% 5-year survival rate in patients with a delayed (>3 years) onset of period. We present a case of stage IIIB cervical squamous cell carcinoma with PRD detected 6 months after radiotherapy. The patient is still tumor free 8 years after radiotherapy. In the light of this patient, we review the literature and discuss the relationship of PRD with survival in the cervical carcinomas.

Treatment results and prognostic factors in oral tongue cancer: analysis of 80 patients.

Treatment results and prognostic factors for 80 patients with oral tongue cancer admitted to Istanbul University Oncology Institute between 1987 and 2000 were retrospectively analysed. The patients were treated by surgery and postoperative or curative radiotherapy. Median age was 55 (22-93) out of which 41 patients (51%) were male and 39 (49%) were female. One patient (1%) had stage I disease, 28 patients (36%) stage II, 18 patients (23%) stage III and 32 patients (40%) stage IVA disease. Nineteen patients (24%) were medically inoperable or refused surgical treatment, so were treated with curative radiotherapy to a total dose of 70Gy (group A). The remaining 61 patients (76%) were treated with surgery and postoperative external beam radiotherapy (group B). The median follow-up time was 44 months. The 5-year overall and loco-regional disease-free survival rates were 42% and 46%, respectively. The 5-year overall survival rates were 16% in group A and 49% in group B (P=0.0002). The 5-year disease-specific survival rate was 23% in group A while in group B it was 49%; the difference was statistically significant (P=0.02). Combined treatment improves overall and disease-free survival in patients with stage II, III and IVA oral tongue cancer. In patients who are not candidates for surgery, the effect of radiotherapy may be increased with the use of brachytherapy.

Postoperative hypofractionated radiotherapy in glioblastoma multiforme.

PURPOSE: To evaluate the safety and efficacy of hypofractionated radiotherapy (HRT) in glioblastoma multiforme (GM) patients in terms of overall and progression-free survival. PATIENTS AND METHODS: Adult patients with GM were prospectively treated with HRT after total, subtotal or partial tumor excision. HRT was applied 3 days a week with a tumor dose of 3.33 Gy per fraction. At the first phase of treatment 12 fractions and at the second phase 3 fractions with smaller fields were delivered. The total dose was 50 Gy/15 fractions/5 weeks. The results were compared with a historical control group of GM patients treated with conventional RT. RESULTS: 20 patients with GM were treated between 1997-2000 at our department. The tumor was multifocal in one (5%) case. The types of operations used were total tumor excision 10(50%) cases, subtotal excision 5 (25%) cases and partial excision 5 (25%) cases. For the historical control group the corresponding operations were 19 (56%), 6 (18%) and 9 (26%). In the study group one-year survival was 50% and median survival 12 months. Mean overall survival was 13.5 (11.3 months for the historical control group, p=0.16) and progression-free survival 6.8 months (5.6 for the historical control group, p=0.36). Treatment was well tolerated. Acute toxicity was minimal and only one HRT patient had late toxicity (brain necrosis). CONCLUSION: The mean overall survival with HRT was better but statistically non significant compared with the historical control group. Our study supports that HRT can be used instead of conventional and hyperfractionated radiotherapy and studies of HRT with higher doses may be meaningful.

Cerebellar and multiple spinal hemangioblastomas and intraventricular meningioma managed with subtotal resection and external beam radiotherapy; report of a case with literature review.

Hemangioblastomas are cystic, highly vascular benign neoplasms that constitute 1.5-2.5% of all intracranial tumors and 7-10% of primary posterior fossa tumors. They occur sporadically (80%) or in association with von Hippel-Lindau (VHL) disease (20%). This disease consists of multiple intracranial, retinal and spinal hemangioblastomas, pheochromocytoma, retinal angiomas, pancreatic cysts, renal cell carcinomas and adrenal tumors. Our patient was a 21-year-old male who presented with cerebellar and multiple spinal hemangioblastomas, and intraventricular meningioma. There was a positive family history (mother and brother) of VHL disease. Intracranial and spinal lesions were treated with external beam radiotherapy following subtotal excision of the cerebellar lesion. Three-year follow-up revealed radiologically stable lesions. Microsurgical resection remains the treatment of choice for the vast majority of symptomatic and sporadic cystic hemangioblastomas. However, since hemangioblastoma is a highly vascular tumor and local invasion of critical structures is frequent and multifocality is often a characteristic of the hemangioblastomas that are associated with VHL disease, subtotal excision is frequent and adjuvant therapies such as external beam radiotherapy or stereotactic radiosurgery represent a reasonable treatment in such cases.

The results of concomitant and sequential chemoradiotherapy with cisplatin and etoposide in patients with locally advanced non-small cell lung cancer.

PURPOSE: To report on the treatment results and demographic characteristics of patients with locally advanced non small cell lung carcinoma (NSCLC) who were treated with concomitant or sequential chemoradiotherapy. PATIENTS AND METHODS: 132 patients with locally advanced NSCLC (stage IIIB) were evaluated. Their median age was 60 years (range 33-80). Histopathological diagnosis was epidermoid carcinoma in 96 (73%) patients, adenocarcinoma in 33 (25%) patients and large cell carcinoma in 3 (2%) patients. Karnofsky performance status (KPS) score was >/= 70 in 112 (85%) patients. Weight loss was greater than 5% in 34 (26%) patients at presentation. One hundred and six (80%) patients were treated with sequential chemoradiotherapy which consisted of 3 monthly cycles of cisplatin (100 mg/m(2), day 1) and etoposide (100 mg/m(2)/day, days 1-3) before radiotherapy. Radiotherapy consisted of a total dose of 60 Gy in 30 fractions (2 Gy / fraction), given to a volume including primary tumor and mediastinum. Two to 4 cycles of chemotherapy were administered after completion of radiotherapy to patients whose disease had not progressed after initial chemotherapy. Twenty-six patients were treated with concomitant chemoradiotherapy. The same radiotherapy regimen was started with the 2nd cycle of chemotherapy which consisted of cisplatin (80 mg/m(2), day 1) and etoposide (100 mg/m(2)/day, days 1-3). Chemotherapy was completed after 4 cycles in all patients. RESULTS: Overall survival (OS) was 14.5 months in 106 patients treated with sequential chemoradiotherapy and 14.6 months in 26 patients treated with concomitant chemoradiotherapy (p=0.99). Median time to progression was 9.77 months in the concomitant group and 11.6 months in the sequential group (p=0.47). However, progression-free survival was better in patients of both groups whose KPS was >70 (12.4 months versus 11.5 months, p= 0.02). While presence of anemia was found as an adverse prognostic factor only in univariate analysis, non-epidermoid histology, KPS less than 70 and presence of N2-N3 disease were found as adverse prognostic factors in both univariate and multivariate analysis. CONCLUSION: The addition of chemotherapy to radiation concomitantly or sequentially prolongs survival in locally advanced NSCLC patients with acceptable adverse event profiles in both arms compared with results of the trials in the literature in which radiotherapy is used as single treatment modality.

The effect of epithelial and myoepithelial differentiations on survival in a parotid gland undifferentiated carcinoma: case report and review of the literature.

Undifferentiated carcinoma of the parotid gland is a rare tumor, with an incidence of 5-10% among all parotid tumors. Salivary gland tumors frequently present myoepithelial cell differentiation. Recognition of myoepithelial cell differentiation is not easily apparent on routinely stained sections and it often requires immunohistochemical or ultrastructural studies. The relationship between these differentiations and survival is still not clear. We report on a 71-year-old male with left parotid undifferentiated small cell carcinoma with epithelial and myoepithelial differentiation that relapsed at the parotid region and neck nodes 4 years after he had undergone superficial parotidectomy. The relapsing disease was treated with total parotidectomy and radical left neck dissection. Also, postoperative radiotherapy was given to the left parotid region and the neck. In total, he is alive 8.5 years from the beginning of the disease, and 54 months after the second surgery and radiotherapy. No disease recurrence has occurred ever since. Undifferentiated carcinomas with epithelial and myoepithelial differentiation are rarely seen and differential diagnosis should be made with salivary gland myoepitheliomas and epithelial-myoepithelial carcinomas. Better understanding of the impact of these differentiations on survival will come with the evaluation of more cases of this unusual malignancy.

Unusual metastases from rectal adenocarcinoma; report of two cases with literature review.

Two case reports of patients with skin and orbital metastasis from rectal carcinoma are described. The reasons for the rarity of this kind of metastases are considered. The survival of these cases was very short.