Journal Issue: Vol. 11, No. 4 - October 2012

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Dr. Kentaro Nakayama



Clinical Relevance of Hif-1a, Cox-2, Leptin, and Prolactin as Hypoxic Markers in Breast Cancer

Dr El-Abd Eman, Dr Hassan A , Dr Faied W , Dr Zaki S , Dr Sobhi A , Dr El-Swedy S , Mr Fatema Soliman

  1. Dr El-Abd Eman
    Associate professor, Molecular Biology Department, Medical Technology Center, rnMedical Research Institute, Alexandria, Egypt.rnTel:+203 4266215,+203 4266216, Fax:+203 4266214, E-mail:,
  2. Dr Hassan A
    Professor, Applied Medical Chemistry Department, Medical Research Institute (MRI), 165, Horreya Avenue, Hadara, Alexandria, Egypt.rn
  3. Dr Faied W
    Associate Professor, Experimental and Clinical Surgery Department, Medical Research Institute, 165, Horreya Avenue, Hadara, Alexandria, Egypt.
  4. Dr Zaki S
    Associate Professor, Cancer Management and Research Department, Medical Research Institute, 165, Horreya Avenue, Hadara, Alexandria, Egypt.rn
  5. Dr Sobhi A
    Associate Professor, Pathology Department, Medical Research Institute, 165, Horreya Avenue, Hadara, Alexandria, Egypt.rn
  6. Dr El-Swedy S
    Professor, Applied Medical Chemistry Department, Medical Research Institute, 165, Horreya Avenue, Hadara, Alexandria, Egypt.rn
  7. Mr Fatema Soliman
    Ameriah Pharmaceutical Company, Alexandria, Egypt.

Background: Hypoxia is a critical event in tumor neovascularization process. It affects prolactin (PRL) and stimulates hypoxia-inducible factor-1α (HIF-1α) which can induce other genes such as cyclooxygenase-2 (Cox-2) and leptin (LEP). Methods: The study included 20 patients with breast cancer and 20 controls. Breast cancer and normal tissues were collected at surgery. Cox-2 gene expression was detected using RT-PCR and nuclear accumulation of HIF-1α protein was detected using dot blot. Both LEP and PRL were detected by ELISA. Tumor angiogenesis was evaluated by IHC using CD31 monoclonal antibody. Results: Cox-2 over-expression was detected in 50% (10/20) of breast cancer specimens. Angiogenesis significantly increased in Cox-2 positive tumors (p = 0.05). HIF-1α nuclear accumulation was observed in 70% of Cox-2 positive tumors and significantly associated with metastasis (p = 0.038). Serum LEP and PRL significantly elevated in patients than controls (p < 0.001). Interestingly, a negative correlation was observed between serum LEP level and the number of the involved LNs in Cox-2 negative tumors (r = -0.751, p = 0.012). Conclusion: HIF-1a and Cox-2 are linked with more aggressive phenotypes of breast cancer. Selective inhibitors for HIF-1a and Cox-2 and antagonists for LEP and PRL might improve prognosis.

Intercomparison of Tamoxifen and Exemestane Hormone Treatment in Receptor Positive Breast Carcinoma Patients

Dr Subiya Kaneez, Dr Mohd Ashraf, Dr Nazir Khan

  1. Dr Subiya Kaneez
    MBBS, MD Radiation Oncology
    Senior Resident/Registrar, Dept. of Radiation Oncology, SMHS, Srinagar, J&K, India.rn
  2. Dr Mohd Ashraf
    MBBS, MD Radiation Oncology
    Professor, Dept of Radiation Oncology,SKIMS,Srinagar, J&K, India.
  3. Dr Nazir Khan
    MBBS, MD Radiation Oncology.rn
    Associate Professor, Dept of Radiation Oncology,SKIMS,Srinagar, J&K, India.rn

Background and Objectives: Breast cancer is the most common malignancy among US women, and is the second leading cause of cancer death. It is widely accepted that the appropriate use of adjuvant chemotherapy and endocrine therapy improves the disease free and overall survival of patients with breast cancer. Tamoxifen has remained a cornerstone in the endocrine therapy of breast cancer. However several clinical trials have revealed several limitations of tamoxifen in adjuvant setting, including limited duration of effectiveness, continuing risk of recurrence, acquired resistance to tamoxifen and serious side effects. Hence, a relatively new class of endocrine therapeutics, the third generation aromatase inhibitors, has been investigated as the potential therapy in the adjuvant setting. Based on results of multiple large randomized controlled trials, we have endeavoured to undertake this study to compare the results of tamoifen and exemestane. Materials: Two groups of 20 patients each were taken for the study. All patients were postmenopausal /post chemopausal and receptor positive. Group 1 received 25 mg’s Exemestane daily for 2 years after having completed Tamoxifen 20 mg’s daily for 3 years and Group 2 patients had taken tamoxifen 20 mg’s daily for 5 years. Patient characteristics in both the treatment arms were comparable. Results: The most common side effect in both the groups was musculoskeletal. 5 year DFS and Response to treatment were better in exemestane group compared to Tamoxifen group, but the results were not statistically significant. Median OS was comparable in both the groups. Conclusion: Exemestane tends to cause fewer side effects than Tamoxifen but more bone loss and fractures than Tamoxifen, at least for first few years of treatment. Switching treatment to exemestane after 3 years of Tamoxifen improves disease free survival and translates into a modest reduction in risk of death.

Invasive Ability in Chordoma

Dr Takahiko Naka

  1. Dr Takahiko Naka
    MD, PhD.rn
    Department of Orthopaedic Surgery, Kyushu Rosai Hospital

Chordoma is an uncommon malignant bone tumor that originates from the remnants of embryonic notochord. Chordoma frequently recurs after excision, which suggests its locally strong invasive ability. Expression of tumor-associated proteinases, including matrix metalloproteinases-1 and –2, cathapsin B and K, urokinase type plasminogen activator, have been shown to have an important role in invasive growth in chordoma. Some of them are elevated in invasion fronts or correlated with the expression of low-molecular-weight cytokeratin and prognosis. Cell adhesion molecules also contribute to the invasive growth of chordoma with both epithelial and mesenchymal characters. Decreased E-cadherin expression and increased N-cadherin expression is considered to lead to the tumor aggressiveness of chordoma. Chordoma frequently expresses c-met proto-oncogene product, c-MET. c-MET expression correlates with proteinase expression, which indicates the role of c-MET in the invasive growth of chordoma.

Radiobiological Impact of Acuros XB Dose Calculation Algorithm on Low-Risk Prostate Cancer Treatment Plans Created by RapidArc Technique.

Dr Suresh Rana

  1. Dr Suresh Rana
    Department of Medical Physics, ProCure Proton Therapy Center, 5901 West Memorial Road, rnOklahoma City

Objective: The purpose of this study was to assess the radiobiological impact of Acuros XB dose calculation algorithm (AXB) on prostate cancer treatment plans created by RapidArc technique. Materials and Methods: A computed tomography (CT) dataset of ten patients with low-risk prostate cancer was selected for this retrospective study. The delineation of prostate, seminal vesicles and organs at risk (OARs) was done on the axial CT images. The treatment plans were created for 6 MV photon beam using RapidArc technique in the Varian Eclipse treatment planning system. The initial dose calculations on treatment plans were performed with Anisotropic Analytical Algorithm (AAA). Next, AXB plans were created by performing dose re-calculation using AXB for same number of monitor units and identical beam set up as in the corresponding AAA plans. Radiobiological modeling response evaluation was done by calculating Niemierko’s Equivalent Uniform Dose (EUD)-based Normal Tissue Complication Probability (NTCP) and Tumor Control Probability (TCP) values. Additionally, the PTV coverage in AXB and AAA plans was evaluated. Results: The averaged TCP values of AAA plan (98.39%) and AXB plans (98.26%) were comparable with difference of 0.14% (P = 1.580 × 10-7). The averaged NTCP values for bladder (P = 0.265) and femur heads (P = 0.281) were well below 0.1 % with no statistical significant differences. However, the averaged NTCP values for the rectum of 0.56 % (AAA) vs. 0.48 % (AXB) suggested the statistical significance (P = 8.741 × 10-3). The PTV coverage in AXB plans was lower by an average 0.89% compared to AAA plans with no statistical significance (P = 0.254). Conclusion: Both the AAA and AXB predicted comparable NTCP and TCP values for low-risk prostate cancer plans created by RapidArc technique. The reduced PTV coverage due to dose re-calculation from AAA to AXB was observed.

Myxoid Neurothekeoma: A Rare Soft Tissue Tumor of Hand in a Male Toddler

Dr Kafil Akhtar, Dr Sufian Zaheer, Dr Prasenjit Ray, Dr. Rana K. Sherwani

  1. Dr Kafil Akhtar
    Department of Pathology, AMU, ALIGARH
  2. Dr Sufian Zaheer
    Department of Pathology, AMU, ALIGARH
  3. Dr Prasenjit Ray
    Department of Pathology, AMU, ALIGARH
  4. Dr. Rana K. Sherwani
    Department of Pathology, AMU, ALIGARH

Neurothekeomas are rare, benign neoplasms, typically occurring in younger patients with a remarkable predilection for the female population. Patients usually present with a small nodule in different anatomical sites, commonly involving the face and the upper limb. We present the case of a three year old boy, who presented with a nodule on the left thumb. Surgical biopsy and immunostaining confirmed the diagnosis of myxoid neurothekeoma. The nomenclature and derivation of these tumors is controversial. The rarity of this unusual skin tumor in a toddler and in daily routine histopathologic findings prompted the following report.

Underlying Genetic Defects in Diseases of Sexual Development in the Island of Cyprus Support the Founder Effect

Dr Nicos Skordis

  1. Dr Nicos Skordis
    Department of Molecular Genetics, Function and Therapy, The Cyprus Institute of Neurology & Genetics

Hereditary endocrinopathies in Cyprus exhibit evidence of a founder effect and display the influence of past migration patterns. The genetic frequency and mutation pattern of specific Disorder of Sex Development (DSD) which is classified as 46, XX DSD or 46, XY DSD and the Non-Classic form of Congenital Adrenal Hyperplasia (NC-CAH) outline a type of genetic drift. The high prevalence of the NC-CAH p.V281L mutation but also the rarity of CAH large lesions present genetic diversity similar to that observed in the Middle Eastern countries. In addition, the high frequency of the 5-alpha Steroid Reductase Deficiency (5αSRD) IVS1-2A>G mutation and the carrier frequency of 17-beta Hydroxysteroid Dehydrogenase 3 (17β-HSD-3) p.R80Q mutation are both good examples of founder effect. The mutation p.R80Q can be considered as a founder mutation even though it has been identified in patients of Dutch, Brazilian and Portuguese origin. This has led to the speculation that it has a Phoenician origin. Phoenicians as ancient traders migrated around 750 B.C from present day Syria, Lebanon and Israel toward Portugal, Spain and also to nearby Cyprus. While the 5αSRD IVS1-2A>G mutation has already been extensively reported in Turkish patients it is very common in the Eastern Mediterranean region. This work portrays clearly, through specific endocrine genetic disorders, the past migrational trends in Cyprus that shaped the present day gene pool of the Greek-Cypriot population.

An Open Labeled Two Arm Study to Evaluate the Feasibility, Quality of Life, Safety and Efficacy of Darbepoetin as Compared to Erythropoietin Inpatients with Chemotherapy Induced Anemia in Patients wit

Dr AVS Suresh, Dr B B Ananda, Dr Chinna Babu S, Dr. Kamireddy Suresh

  1. Dr AVS Suresh
    Department of Medical Oncology, BIBI General Hospital and Cancer Centre
  2. Dr B B Ananda
    Department of Surgical Oncology, BRA Medical College, Bangalore.rn
  3. Dr Chinna Babu S
    Department of Clinical Research, ClinSync, Hyderabad
  4. Dr. Kamireddy Suresh
    Department of Clinical Research, ClinSync, Hyderabad

Aim: An open labeled two arm study to evaluate the feasibility, quality of life, safety and efficacy of Darbepoetin as compared to Erythropoietin in patients with chemotherapy induced anemia of Gastro intestinal malignancies. Methods: This study was conducted in two hospitals in patients with metastatic GI malignancies who have chemotherapy induced anaemia. The selection of GI malignancies is due to lack of EPO receptors in malignant cells, there by reducing the adverse risk of erythropoietic agents on disease outcomes. The subjects have received chemotherapy and erythropoietic agents as per standard guidelines. Results: A total of 42 patients with chemotherapy induced anaemia were randomized in 1:1 ratio to either Darbepoetin or conventional erythropoietin arms. Darbepoetin has shown to improve the Health related Quality of Life when compared to erythropoietin. There is no statistically significant differences in the mean raise of haemoglobin during the study period or cost of therapy or incidence of adverse events in either arms. Conclusion: The current study indicates that it is feasible to give either of the erythropoietic agents in the gastrointestinal cancer patients with chemotherapy induced anaemia and there are no differences among the Darbepoetin or conventional erythropoietin. Though the current study is not designed or powered to evaluate the disease free survival compared to historical controls, it appears that administration of erythropoietic agents as per standard guidelines do not affect the disease outcomes in gastro intestinal malignancies.

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