Circulating osteocyte-related biomarkers (vitamin D, sclerostin, dickkopf-1), hepcidin, and oxidative stress markers in early breast cancer: Their impact in disease progression and outcome.

Breast cancer (BC) is a major concern to female health worldwide. We assessed the circulating osteocyte-related biomarkers, hepcidin, and oxidative stress status among early-stage BC patients in aspects of clinical severity and impact on the outcome. The study incorporated 73 patients categorized into 57 early-stage BC and 16 benign breast diseases and 30 healthy controls. Serum 25-hydroxyvitamin D [25(OH)D], sclerostin (SOST), dickkopf-1(DKK1), and hepcidin were measured using ELISA, while, serum oxidative stress markers were assessed by spectrophotometry. Our results show that patients with BC showed significant increase in the mean levels of DKK1, SOST, hepcidin, and LPER and significant decrease in the mean levels of 25(OH)D, SOD, GPx, and Hb when compared with controls and benign breast diseases. Significantly higher DKK1, hepcidin, and SOD levels among benign breast diseases were found in comparison to control group. There were significantly lower levels of 25(OH)D, SOD, and Hb and significantly higher levels of SOST, DKK1, hepcidin, No, and LPER with advanced grade. Lower levels of 25(OH)D, SOD and higher levels of SOST, hepcidin were observed with increasing the malignant stage. Reduced levels of 25(OH)D, and SOD were significantly associated with poor prognosis and were strong predictors among BC. There were significant negative correlations between 25(OH)D with LPER, SOST, and hepicidin. We conclude that low 25(OH)D, high SOST, DKK1, and hepcidin, and dysregulated oxidative stress could be helpful in early detection and assessment of BC. 25(OH)D, and SOD were the most relevant to tumor progression and prognosis which indicate a significant role in the BC pathogenesis and could be promising targets in management. Our research paves the way to disrupt vicious circle between these biomarkers to obtain the best care of BC.

Tissue Indices of Telomere Length and p53 in Patients with Different Gastrointestinal Tumors: Correlation with Clinicopathological Status.

Telomere length dysfunction is involved in the generation of genomic rearrangements that drive progression to malignancy. A set of serological markers for telomere dysfunction, namely chitinase and N-acetylglucosaminidase (NAG), DNA damage, and tissue alteration of p53 have been identified. The probability that genomic damage, accumulation of reactive oxygen species, and shorter telomeres may be related to the onset and advancement of gastrointestinal (GI) tumors. A total of 40 patients with GI tumors and 20 healthy controls with matched age and sex were included. Estimation of serum chitinase, NAG, lipid peroxide (LPER), glutathione peroxidase (GPx), superoxide dismutase (SOD), catalase by colorimetric methods, and p53 by ELISA were assessed. Related clinicopathological features were determined. Serological chitinase, NO, LPER, and p53 were significantly increased, SOD was significantly decreased (p Ë‚ 0.001 for each) in GI tumor patients compared with controls and correlated significantly with age. There was a significant correlation between telomere dysfunction indices, p53, oxidative stress indices, and malignant stages of GI cancer patients. Moreover, a significant difference in the mean serum levels of indices between control, malignant, and benign subjects was found. Accordingly, these biomarkers play an important role in the pathogenesis of GI cancer and their estimation may predict the GI tumor behavior.

Apoptosis, angiogenesis, inflammation, and oxidative stress: basic interactions in patients with early and metastatic breast cancer.

PURPOSE: Breast cancer (BC) is a complex, multi-stage disease involving deregulation of different signaling cascades. The present study was conducted to determine the extent of apoptosis, angiogenesis, inflammation, and oxidative stress in patients with different stages of BC as an approach to disease biological behavior. Therefore, plasma levels of soluble (s) Fas, bcl-2 as antiapoptotic indices; interleukin (IL)-8, tumor necrosis factor (TNF)-α as apoptotic, inflammatory, angiogenic indices; lipid peroxides (LPO), nitric oxide (NO) as oxidative stress and angiogenic indices were measured in patients with BC. METHODS: Thirty-seven newly diagnosed patients with BC, 30 patients with benign breast masses, and 30 healthy controls were recruited. Plasma levels of sFas, bcl-2, IL-8, and TNF-α were measured by immunosorbent assay kits and LPO and NO by chemical methods. RESULTS: Plasma sFas and LPO were significantly higher in BC patients versus benign breast masses and healthy controls (P < 0.0001). Bcl-2, IL-8, TNF-α, and NO were significantly higher in benign breast masses (P < 0.0001, P < 0.037, P < 0.0001, P < 0.001) and BC (P < 0.0001) versus controls and in BC versus benign breast masses (P < 0.0001). sFas, bcl-2, IL-8, TNF-α, LPO, and NO were increased with advanced tumor stages. There were positive correlations between sFas, bcl-2, IL-8 TNF-α, LPO, and NO. CONCLUSIONS: BC tumor cells overexpress bcl-2 and sFas to secure their outgrowth and survival. However, this coincides with activation of physiologic regulatory mechanisms, as increased IL-8, TNF-α, LPO, and NO, which try to stop tumor cells by inducing apoptosis. Outcompeting of these mechanisms result in tumor progression as IL-8, TNF-α, and NO are also angiogenic stimulators.

Biological markers and response to neoadjuvant taxane-based chemotherapy in patients with locally advanced breast cancer.

Introduction. Biological markers as Her2/neu, p53, and hormonal receptors (HmRs) may be reliable parameters for prognostic assessment of patients of locally advanced breast cancer (LABC). This work aims at assessing the potential value of these biological markers for the prediction of disease outcome after neoadjuvant taxane-based chemotherapy and its implication on the surgical role. Patients and Methods. From March 2006 to September 2011, 95 patients with LABC were treated by neoadjuvant taxane-based chemotherapy given at intervals of 3 weeks. Expression of Her2/neu and p53 was examined in the initial tissue biopsy by using ELISA technique. Status of HmRs was determined using a commercial enzyme immunoassay. Three weeks after the third cycle, patients underwent surgical resection followed by 3 more cycles of taxane-based chemotherapy and radiotherapy as an adjuvant therapy. Relations of Her2/neu overexpression to p53, HmRs, and conventional prognostic factors were analyzed. Results. Median followup was 61 months. The 5-year DFS and OAS rates were significantly higher in patients with positive HmRs than in those with negative HmRs, patients with Her2- than those with Her2+ breast cancer, and patients with intact p53 breast cancer than those with inactive p53. HER-2 overexpression was statistically significant associated with loss of HmR positive immunostaining (P < 0.0001), grade III breast cancer (P < 0.0001), advanced nodal status (P = 0.0039), and younger (<50 years) age (P = 0.0108). Conclusion. Her2/neu overexpression was associated with poor DFS and OAS rates, as it was significantly associated with negative HmR and high grade.

Feasibility of breast conservation after neoadjuvant taxene based chemotherapy in locally advanced breast cancer: a Prospective Phase I trial.

BACKGROUND: Neoadjuvant chemotherapy is the standard care for locally advanced breast cancer. Our study aimed at evaluating the feasibility of breast conversation surgery (BCS) after neoadjuvant chemotherapy. PATIENTS AND METHODS: Forty five patients had stage IIB (except those with T2N1 disease) and stage IIIA were selected to 3 cycles taxane-based neoadjuvant chemotherapy. Patient who had tumours ≤5 cm underwent a tentative BCS while patients who had tumour size >5 cm underwent radical surgery. Negative margin is essential for BCS. Adjuvant chemotherapy and 3-D radiotherapy ± hormonal treatment were given to all patients. RESULTS: Thirty four patients had BCS. Response to chemotherapy was the only statistically significant factor which influences the BCS. Incidence of local recurrence was 5.9% for patients who had BCS at a median follow up 24 months. CONCLUSION: Breast conservation is feasible in selected cases of locally advanced, non metastatic cancer breast. We recommend that patients who have tumour size ≤4 cm after chemotherapy are the best candidates for BCS.

Surgical treatment for locally advanced lower third rectal cancer after neoadjuvent chemoradiation with capecitabine: prospective phase II trial.

INTRODUCTION: Treatment of rectal cancer requires a multidisciplinary approach with standardized surgical, pathological and radiotherapeutic procedures. Sphincter preserving surgery for cancer of the lower rectum needs a long-course of neoadjuvant treatments to reduce tumor volume, to induce down-staging that increases circumferential resection margin, and to facilitate surgery. AIM: To evaluate the rate of anal sphincter preservation in low lying, resectable, locally advanced rectal cancer and the resectability rate in unresectable cases after neoadjuvent chemoradiation by oral Capecitabine. PATIENTS AND METHODS: This trial included 43 patients with low lying (4-7 cm from anal verge) locally advanced rectal cancer, of which 33 were resectable. All patients received preoperative concurrent chemoradiation (45 Gy/25 fractions over 5 weeks with oral capecitabine 825 mg/m2 twice daily on radiotherapy days), followed after 4-6 weeks by total mesorectal excision technique. RESULTS: Preoperative chemoradiation resulted in a complete pathologic response in 4 patients (9.3%; 95% CI 3-23.1) and an overall downstaging in 32 patients (74.4%; 95% CI 58.5-85). Sphincter sparing surgical procedures were done in 20 out of 43 patients (46.5%; 95% CI 31.5-62.2). The majority (75%) were of clinical T3 disease. Toxicity was moderate and required no treatment interruption. Grade II anemia occurred in 4 patients (9.3%, 95% CI 3-23.1), leucopenia in 2 patients (4.7%, 95% CI 0.8-17) and radiation dermatitis in 4 patients (9.3%, 95% CI 3-23.1) respectively. CONCLUSION: In patients with low lying, locally advanced rectal cancer, preoperative chemoradiation using oral capecitabine 825 mg/m2, twice a day on radiotherapy days, was tolerable and effective in downstaging and resulted in 46.5% anal sphincter preservation rate.

Preoperative gemcitabine based chemo-radiotherapy in locally advanced non metastatic pancreatic adenocarcinoma.

INTRODUCTION: Almost 30% of patients with pancreatic cancer have locally advanced tumours in absence of distant metastasis. Surgical resection is often contraindicated. The combination of gemcitabine with concurrent radiation therapy is a promising new approach that is being investigated for treating patients' unresectable pancreatic cancer. This work aims at assessing the efficacy of preoperative gemcitabine based chemo-radiotherapy in increasing the resectability rate for patients' locally advanced pancreatic cancer. PATIENTS AND METHODS: From March 2006 to November 2007, 25 patients with locally advanced non metastatic pancreatic cancer were treated by preoperative gemcitabine based chemo-radiotherapy. The radiation dose was 54 Gray in 30 fractions over 6 weeks prescribed to the isocenter. Gemcitabine (300 mg/m2) was given through a 30 minute intravenous infusion. This was done 30 minutes before the radiation sitting on a weekly basis throughout the radiotherapy course.Approximately 6 weeks after the completion of chemo radiation, an evaluation was performed regarding tumour response and resectability as well as acute toxicity. Pancreaticoduodenectomy was performed for operable patients with surgical reconstruction. RESULTS: Patients who achieved complete resection (CR) numbered 2 (8%), while those achieving partial resection (PR) totalled 11 (44%); six of these patients were considered ro be operable. Thus Pancreaticoduodenectomy was performed on 8 patients (2 with CR and 6 with PR) with surgical reconstruction. Patients who had a stable disease numbered 4 (16%), and those with progressive diseases included a group of eight (32%). The postoperative 30 day mortality occurred only in one patient (12.5%). Acute toxicity of chemoradiation occurred in the form of grade I leucopoenia and thrombocytopenia. Hepatic toxicity, nausea, and vomiting were found in 8 patients (32%), 10 patients (40%) and 4 patients (16%), respectively. The postoperative 30 day mortality occurred only in 1 patient. Also, minor biliary leakage and leakage from gastrointestinal anaestomosis both occurred in a single patient. Out of the 8 patients who underwent radical surgical resection, only one developed local recurrence and simultaneous liver metastasis during the follow up period. The median survival of all patients was 12 months. CONCLUSION: Preoperative gemcitabine based chemoradiation might benefit patients with locally advanced non metastatic pancreatic cancer by increasing the resectability without significant acute toxicity.

Fetus in fetu: a case report.

INTRODUCTION: Fetus in fetu is a rare abnormality secondary to the abnormal embryogenesis in a diamniotic, monochorionic pregnancy. It is a rare pathological condition and fewer than 100 cases have been reported in the literature. CASE PRESENTATION: A 2 month old girl with an abdominal mass since birth, was referred to the Cancer Institute with a suspected diagnosis of a Wilms' tumor. Conventional radiograph of the abdomen revealed a mass containing numerous calcifications. CT scan showed a heterogeneous retroperitoneal mass containing well-defined calcified structures. The decision was made to recommend surgical exploration and the mass was successfully excised. Physical examination of the mass with review of literature confirmed the diagnosis of fetus in fetu. CONCLUSION: Although it is a rare condition imaging may play an important role in the correct prospective diagnosis of fetus in fetu. Surgical excision is the recommended treatment.