bluuebunny/crossref_metadata_2025 huggingface dataset:
Mutation Analysis of the FHIT Gene in Bronchoscopic Specimens from Patients with Suspected Lung Cancer
Authors: Cecener Gulsah , Tunca Berrin , Egeli Unal , Karadag Mehmet , Vatan Ozgur , Uzaslan Esra , Tolunay Sahsine
Published: February 2018

Aims and Background

Lung cancer is a leading cause of cancer death worldwide. However, despite recent advances in molecular biology that have revealed various genetic changes in lung cancer, the prognostic outcome of lung cancer patients has improved only minimally. This situation has changed fundamentally with the identification of molecular abnormalities that are characteristic of premalignant changes, such as changes in tumor suppressor genes, loss of heterozygosity at crucial sites, and activation of oncogenes. Inactivation of the tumor suppressor gene Fragile Histidine Triad (FHIT) is a frequent genetic change in lung cancer. The aim of this study was to identify FHIT gene alterations in bronchoscopy specimens of patients with suspected lung cancer and to determine the molecular relevance, if any, of FHIT alterations in the development of cancer.

Patients and Methods

Sixty-two patients with suspected lung tumors were screened for variations within exons 5-9 of the FHIT gene using intronic primer pairs and single-strand conformation polymorphism and sequencing analysis.

Results

FHIT gene alterations were detected in 27 out of 62 bronchoscopic specimens (43.54%). All of these alterations were identified as T to A alteration at position IVS8-17. This intronic variant also was identified in approximately half of control cases (45%).

Conclusions

Our findings showed that the FHIT IVS8-17 T to A alteration identified in bronchoscopy specimens from patients with clinically suspected lung cancer is a polymorphism found in the Turkish population. We think that this polymorphism does not affect gene function because it is located in the intron portion of the gene and is present in many cancer patients as well as healthy subjects. We suggest that the FHIT gene may be turned off in lung carcinogenesis via other genetic or epigenetic mechanisms rather than mutations.
Cervical Chordoma with Retropharyngeal Extension Presenting with Impaired Voice
Authors: Nicoucar Keyvan , Rausch Thierry , Becker Minerva , Dulguerov Pavel
Published: February 2018

Aims and Background

We report an extremely rare case of cervical chordoma presenting with impaired voice.

Method

Case report and a review of the literature concerning the presentation, diagnosis, and treatment of a cervical chordoma.

Results

A singing teacher complaining of dysphonia was examined and surgically treated for a retropharyngeal extension of a cervical chordoma. A local recurrence was treated with proton beam therapy. Among primary malignant tumors of bone, chordomas account for 3–4% of all cases. Chordoma is typically a locally aggressive tumor with a high propensity for local recurrence. Its management involves surgery, radiotherapy, or both.

Conclusion

To our knowledge this is the first report in the world literature of a retropharyngeal extension of a cervical chordoma presenting with impaired voice. This case indicates that bony tumors of the spine may present first to voice-disorder clinicians. Increased awareness of this neoplasm may lead to earlier diagnosis and better treatment.
Symptomatic Leptomeningeal and Intramedullary Metastases from Intracranial Glioblastoma Multiforme: A Case Report
Authors: Scoccianti Silvia , Detti Beatrice , Meattini Icro , Iannalfi Alberto , Sardaro Angela , Leonulli Barbara Grilli , Martinelli Francesco , Bordi Lorenzo , Pellicanò Gianni , Biti Giampaolo
Published: February 2018

Background

Glioblastoma multiforme infrequently metastasizes to the leptomeninges and even more rarely to the spinal cord. Moreover, very few patients with intracranial glioblastoma develop symptoms from spinal dissemination, with most patients not surviving long enough for spinal disease to become clinically evident.

Case Report

We present a rare case of symptomatic diffuse spinal leptomeningeal metastases simultaneously to an intramedullary lesion from an intracranial glioblastoma multiforme. After the diagnosis of spinal metastases the patient was treated with limited-field spinal radiotherapy (30 Gy in 3-Gy fractions).

Results

Radiotherapy on the main spinal lesions provided either relief from pain or mild improvement of neurological deficits. The patient died due to intracranial progression 4 months after diagnosis of spinal seeding and 17 months after diagnosis of the primary disease. We analyzed leptomeningeal and spinal metastases from glioblastoma multiforme with reference to the literature.

Conclusions

Radiotherapy for spinal disease may provide important symptom relief but the prognosis of these patients remains dramatically poor. As the local control of primary glioblastoma multiforme has improved with recent therapeutic advances, distant metastasis from high-grade gliomas is likely to become a more common clinical problem and such patients need to be included in clinical trials to evaluate new therapeutic approaches.
Pancreaticoduodenectomy for Dysplastic Duodenal Adenoma in a Patient with Familial Adenomatous Polyposis
Authors: Merenda Roberto , Portale Giuseppe , Galeazzi Francesca , Tosolini Chiara , Sturniolo Giacomo Carlo , Ancona Ermanno
Published: February 2018

Colorectal polyposis is the main feature of familial adenomatous polyposis (FAP), but benign and malignant lesions have also been described in the stomach, duodenum, small bowel, biliary tract and pancreas. There are few reports on FAP patients with duodenal polyps that developed at a younger age and even fewer on cases with dysplastic degeneration. The progression to carcinoma usually presents quite late in the clinical history of FAP patients, typically at least 20 to 25 years after proctocolectomy. This report described the rare case of a patient presenting with duodenal adenomas with dysplastic changes and tumor infiltration as the first sign of FAP, who was treated by pancreaticoduodenectomy followed by proctocolectomy for subsequent dysplastic changes in colonic polyps.
Extraskeletal Ewing's Sarcoma/Primitive Neuroectodermal Tumor of the Posterior Mediastinum with t(11;22)(q24;q12)
Authors: Manduch Marosh , Dexter David F , Ellis Peter M , Reid Kenneth , Isotalo Phillip A
Published: February 2018

Ewing's sarcoma/primitive neuroectodermal tumor family of tumors is part of a rare group of malignant neoplasms with small round-cell morphology. We describe a 24-year-old woman who presented with non-specific back pain. A chest radiograph and magnetic resonance imaging demonstrated an extraosseous, dumbbell-shaped mass of the posterior mediastinum with extension into the spinal canal. The patient underwent a left posterolateral thoracotomy and a T3–5 laminectomy with subsequent multi-agent chemotherapy. Histopathologic examination of the tumor demonstrated sheets of primitive small round malignant cells that showed no visible differentiation. Neoplastic cells were strongly immunoreactive for CD99 and vimentin and were negative for chromogranin, synaptophysin, CD31, CD34, calcitonin, desmin, low-molecular weight cytokeratins, wide-spectrum cytokeratins, leukocyte common antigen, S-100 protein, and thyroid transcription factor-1. The neoplasm was diagnosed as a Ewing's sarcoma/primitive neuroectodermal tumor, and cytogenetic studies confirmed a t(11;22)(q24;q12) chromosomal translocation and an associated trisomy of chromosome 2, supporting the histologic diagnosis. Extraskeletal Ewing's sarcoma/primitive neuroectodermal tumors are rare neoplasms that should be distinguished from other small round-cell tumors by morphology and ancillary laboratory techniques. Although rare, they need to be considered in the differential diagnosis of primary mediastinal tumors.
Gemcitabine and Carboplatin Treatment in Advanced NSCLC: A Retrospective Evaluation Including Elderly Patients
Authors: Murialdo Roberto , Boy Davide , Bertolotti Francesca , Martini Maria Cristina , Pastorino Gisella , Sogno Giorgio , Vallauri Matteo , Moraglio Lorenza , Tixi Lucia , Angelini Isabella , Saccà Vittoria , Ballestrero Alberto , Brema Fulvio
Published: February 2018

Background

Carboplatin-containing regimens are sometimes preferred for patients with advanced non-small cell lung cancer.

Methods

Eighty-three patients with stage III-IV non-small cell lung cancer received 3 to 4 cycles of carboplatin AUC 5 on day 2 and gemcitabine 1250 mg/m2 on days 1 and 8 every 21 days.

Results

The overall response rate was 43.4%. Results obtained from elderly and non-elderly groups were compared using the logrank method. Median overall survival and progression-free survival were 11 and 7 months, respectively (12 and 7 months, non-elderly group; 6.5 and 5 months, elderly group, P = 0.28 and 0.25 respectively). Grade 3–4 toxicity included neutropenia, thrombocytopenia, anemia, nausea/vomiting, and diarrhea. Incidences of grade 3–4 toxicity were similar for elderly and non-elderly patients.

Conclusions

Data confirm that carboplatin-gemcitabine is an active and well-tolerated regimen in advanced non-small cell lung cancer and could be investigated in elderly patients.
Mediastinal Composite Hemangioendothelioma. A Rare Tumor at an Unusual Location
Authors: Cakir Ebru , Demirag Funda , Gulhan Erkmen , Oz Gurhan , Tastepe Irfan
Published: February 2018

Composite hemangioendothelioma is a rare vascular tumor; only 12 cases have been previously described in the extremities, tongue and axilla. We report the first case of composite hemangioendothelioma of the mediastinum in a 50-year-old woman. She was admitted to our hospital with dyspnea and cough lasting for two months. Her chest roentgenogram and computed tomography showed a 6 × 4 × 3 cm mass in the middle mediastinum compressing the trachea. She underwent total sternotomy and resection of the mass. Microscopically the most important feature at low power was the variability in the histological pattern. This case is presented not only for the rarity of the tumor type but also for its unusual location.
Florid Vascular Proliferation in Mature Cystic Teratoma of the Ovary: Case Report and Review of the Literature
Authors: Akbulut Metin , Zekioglu Osman , Terek Mustafa Cosan , Ozdemir Necmettin
Published: February 2018

A case of mature cystic teratoma that contained florid vascular proliferation is reported. The ovarian tumor occurred in a 9-year-old girl; symptoms consisted of vomiting, abdominal pain and a palpable mass. The microscopic findings were mostly typical of a mature cystic teratoma, but also abundant vascular proliferation mimicking hemangioma in association with mature neural tissue was observed. There was a disorganized arrangement of medium- and large-sized spaces lined by cuboidal endothelial cells. Immunohistochemical staining for vascular proliferation showed immunoreactivity for CD31 and smooth muscle actin. Florid vascular proliferation may be seen in association with neural tissue of ovarian teratomas and should not be misdiagnosed as immature teratoma or a vascular neoplasm.
A Case of Ovarian Psammocarcinoma Associated with Endometrioid Cysts: A Morphological and Immunohistochemical Study
Authors: Sanguedolce Francesca , Indraccolo Ugo , Tortorella Simona , Nappi Luigi , Rosenberg Piergiorgio , Greco Pantaleo , Bufo Pantaleo
Published: February 2018

Background

Psammocarcinoma of the ovary is an uncommon neoplasm, currently classified among the low-grade epithelial serous tumors. Little is known about its pathogenesis and biological behavior.

Case

A 35-year-old woman underwent laparotomic myomectomy and surgical removal of the right gonad after the incidental discovery of an adnexal mass. The pathological findings were consistent with serous psammocarcinoma and multiple endometrioid cysts of the ovary. Tissue specimens from the neoplasm were tested by immunohistochemistry for the p53, HER-2/neu and bcl-2 cancer-related proteins; diffuse overexpression for bcl-2 was detected, while tumor cells were negative for p53 and HER-2/neu.

Conclusion

Although the pathogenesis and clinical course of ovarian psammocarcinoma are still to be determined, the molecular profile of this case highlights the similarities with ovarian tumors of the serous borderline group.
Italian Performance in Cancer Research
Authors: Micheli Andrea , Di Salvo Francesca , Lombardo Claudio , Ciampichini Roberta , Ugolini Donatella , Baili Paolo , Pierotti Marco A
Published: February 2018

Aims and background

Italian performance in cancer research from 2000 to 2007 was assessed and compared to that of the other 19 wealthiest countries in the world which carry out the bulk of cancer research.

Methods

Performance was evaluated quantitatively as the number of publications in 125 journals indexed as ‘oncological’ by Journal Citation Reports and qualitatively as the total impact factor (TIF). Number of publications and TIF were adjusted for the population and gross domestic product (GDP) of each country. The Scopus database was used as publication source.

Results

Italy ranked 5th, with the US ranking 1st, over the entire study period for number of cancer publications, which increased over that period. Italy ranked 4th in 2006–2007 for GDP-adjusted and 5th for population-adjusted publication number, loosing ground in the GDP-adjusted ranking and gaining ground in the population-adjusted ranking over the study period. When the quality of research publications was considered, in 2006–2007 Italy was in 5th place for crude TIF (US 1st), in 4th place for GDP-adjusted TIF (Sweden 1st), and in 6th place for population-adjusted TIF (Sweden 1st). Over the study period, Italy was stable for crude and population-adjusted TIF but declined somewhat for GDP-adjusted TIF.

Conclusions

Italy's performance in cancer research over the eight years to 2008 was better than expected considering its GDP and population. Nevertheless, the slight decline evidenced by the present study should induce scientists and policy makers to find ways to reverse the situation.
Outcome of Newly Diagnosed Glioblastoma Patients Treated by Radiotherapy plus Concomitant and Adjuvant Temozolomide: A Long-Term Analysis
Authors: Erpolat Ozge Petek , Akmansu Muge , Goksel Fatih , Bora Huseyin , Yaman Emel , Büyükberber Suleyman
Published: February 2018

Aims and background

Glioblastoma is the most common primary brain tumor in adults. The standard treatment is surgery and radiotherapy. In this study, the results of radiotherapy plus concomitant and adjuvant temozolomide are reported. In addition, the efficiency of adjuvant temozolomide is evaluated.

Methods and study design

Forty-one patients were analyzed. All patients received radiotherapy (2 Gy daily fractionation dose, median 60 Gy total doses) and concomitant temozolomide (at a daily dose of 75 mg/m2/day, 7 days per week) after surgery. Thirty-one patients received an average of 6 cycles (range, 1–8 cycles) of adjuvant temozolomide after radiotherapy, every 28 days for 5 days at a dose of 200 mg/m2/day. The primary end point was overall survival.

Results

The median overall survival was 16.7 months. The overall survival significantly increased in the adjuvant temozolomide group compared to the group with no adjuvant therapy (18.9 vs 9.8 months). The difference in overall survival between adjuvant temozolomide cycles of ≤ and >3 was significant (8.7 vs 20 months). On multivariate analyses, the important prognostic factors were type of surgery and application of adjuvant temozolomide for at least 4 cycles. Grade III/IV toxicity was seen in 4% and 6.5% of patients during concomitant and adjuvant therapy, respectively.

Conclusions

The study confirmed the effectiveness of radiotherapy plus temozolomide in newly diagnosed glioblastoma. It was established that the application of adjuvant temozolomide for at least 4 cycles is required to obtain a benefit from adjuvant therapy. However, further studies are needed to confirm these data.
Cost-Effectiveness of Pegfilgrastim versus Six Days of Filgrastim for Preventing Febrile Neutropenia in Breast Cancer Patients
Authors: Danova Marco , Chiroli Silvia , Rosti Giovanni , Doan Quan V
Published: February 2018

Aims and background

Febrile neutropenia (FN) is a major complication of chemotherapy and is associated with substantial morbidity, mortality and costs. The aim of this study was to evaluate the cost-effectiveness of primary prophylaxis with pegfilgrastim versus six-day filgrastim in preventing FN in Italian patients with early-stage breast cancer receiving adjuvant chemotherapy associated with a ≥20% FN risk.

Methods

The pharmacoeconomic evaluation was based on a decision-analytic model taking into account the possible consequences of FN (e.g., death and reduction/delay of chemotherapy dose). Parameters included in the model were relative risk of FN with pegfilgrastim versus six-day filgrastim; direct costs (drug purchase and FN-related hospitalizations); relative risk of relative dose intensity <85% with pegfilgrastim versus filgrastim; impact on long-term survival due to relative dose intensity <85%; and impact of age on FN and relative dose intensity <85%.

Results

Under base-case assumptions, pegfilgrastim was cost-effective compared to six-day filgrastim in Italy. The estimated cost, life expectancy and quality-adjusted life years per person for pegfilgrastim were € 3078, 16.47 years, and 15.32; the corresponding figures for six-day filgrastim were € 3033, 16.35 years, and 15.22. The corresponding incremental cost-effectiveness ratio with pegfilgrastim was € 409 per life-year gained and € 429 per quality-adjusted life year gained. One-way sensitivity analyses showed that the results were most sensitive to the relative risk of FN for 6-day filgrastim versus pegfilgrastim. The results were moderately sensitive to the cost of pegfilgrastim and filgrastim, cost of drug administration, cost of FN hospitalization, and number of chemotherapy cycles. Pegfilgrastim remained cost-effective, with an incremental cost-effectiveness ratio well below the accepted limit of € 50,000 per life year gained in all one-way sensitivity analyses. A two-way sensitivity analysis on cost of drugs showed a range of pegfilgrastim dominance over six-day filgrastim.

Conclusions

At the current official price in Italy, primary prophylaxis with pegfilgrastim improved health outcomes with a very limited cost increase for the National Health Service payer. Even when very low prices of filgrastim and high prices of pegfilgrastim were considered in the model, the resulting incremental cost-effectiveness ratio remained well within the acceptable cost-effectiveness limit of € 50,000/quality-adjusted life year.
Kaposi's Sarcoma in Young Patients Treated with Orthovoltage Irradiation and Having a Minimum Follow-Up of Forty-Six Years
Authors: Pergolizzi Stefano , Santacaterina Anna , Gaeta Michele , Blandino Alfredo
Published: February 2018

Purpose

To describe the clinical outcome and to evaluate the role of orthovoltage radiotherapy in the treatment of young (less than 30 years old) Mediterranean men with Kaposi's sarcoma.

Patients and methods

We reviewed the records of 198 consecutive patients with Kaposi's sarcoma treated with orthovoltage radiation therapy at our department between January 1920 and December 1987.

Result

We found three young shepherds, aged less than 30 years, with an available follow-up ranging from 45 to 67 years. One patient died at the age of 84 years of chronic renal failure while suffering from cutaneous Kaposi's sarcoma; two patients are still alive with recurrent Kaposi's sarcoma.

Conclusions

We presume that an indolent form of Kaposi's sarcoma may occur in young men. This very indolent form can be controlled for the duration of the patient's life by judiciously applied radiation therapy.
Three-Dimensional Conformal Radiotherapy, Temozolomide Chemotherapy, and High-Dose Fractionated Stereotactic Boost in a Protocol-Driven, Postoperative Treatment Schedule for High-Grade Gliomas
Authors: Pirtoli Luigi , Rubino Giovanni , Marsili Stefania , Oliveri Giuseppe , Vannini Marta , Tini Paolo , Miracco Clelia , Santoni Riccardo
Published: February 2018

Aims and background

No available scientific report deals with high-dose (≥70 Gy) radiotherapy plus temozolomide chemotherapy (TMZ CHT) in high-grade gliomas. The survival results of a protocol-driven, postoperative treatment schedule are reported here to contribute to the discussion on this issue.

Methods and study design

Uniform criteria were prospectively adopted for case selection during the period 1993–2006 in the management of 123 patients, and we progressively introduced three-dimensional conformal radiotherapy (3D-CRT, 60 Gy), TMZ CHT and a high-dose (70 Gy) stereotactic boost (HDSRT) in the treatment schedule. Palliative radiotherapy was delivered by whole brain irradiation (WBI, 50 Gy) for bulky tumors, whereas radical irradiation was performed with 3D-CRT throughout the study period. Two periods of accrual are considered: 36 patients were treated before 31 December 1999 (29.25%) and 87 (70.75%) after 1 January 2000. This subdivision was due to the implementation of HDSRT hardware and TMZ CHT from January 2000.

Results

The median overall survival was 13 months and the 1-, 2- and 3-year survival rates were 53%, 19.5% and 11.6%, respectively. The differences in survival related to the treatment variables were highly significant, both in univariate and multivariate analysis. The median survival and 1-, 2- and 3-year survival rates in the palliative WBI group were 9.75 months and 37%, 2%, and 0%, respectively; in the 3D-CRT group 17.25 months and 64%, 34%, and 15%, respectively; in the TMZ CHT concomitant with radiotherapy group 20 months and 61%, 39%, and 21%, respectively; in the TMZ CHT concomitant with and sequential to radiotherapy group 25.75 months and 84%, 54%, and 26%, respectively, and in the HDSRT group 22 months and 72%, 48%, and 37%, respectively. No symptomatic radiation necrosis occurred in any of the groups.

Conclusions

The results reported here are generally better than those reported in the literature. The selection of patients on the basis of favorable prognostic factors and suitability to the currently available, aggressive postoperative treatment resources can be the mainstay for improving therapeutic results. In particular, the new treatment option reported here (HDSRT in association with TMZ CHT) proved to be safe and effective in obtaining a relatively favorable outcome.
A Fast SSP-PCR Method for Genotyping the ATP-Binding Cassette Subfamily B Member 1 Gene C3435T and G2677T Polymorphisms in Chinese Transplant Recipients
Authors: Wu Cun-Zao , Ni Xiao-jie , Zheng Shao-ling , Yang Yi-Rong , Xia Peng , Zeng Yan-Jun , Chen Bi-Cheng
Published: February 2018

Aim

P-glycoprotein, the product of the ATP-binding cassette subfamily B member 1 (ABCB1) gene (or the so-called multidrug resistance 1 gene), is an ATP-driven efflux pump contributing to the pharmacokinetics as well as the pharmacokinetics of drugs that are P-glycoprotein substrates, such as tacrolimus. This paper describes the development of a new method for detection of the 3435C/T and 2677G/T/A single nucleotide polymorphisms of the ABCB1 gene. The method is a simple sequence-specific primer polymerase chain reaction (SSP-PCR).

Methods

158 Chinese health checkup examinees and 214 transplant recipients were included in the study. Genomic DNA was extracted from peripheral blood and amplified with SSP-PCR to detect the 3435C/T and 2677G/T/A mutations in ABCB1. The SSP-PCR condition was optimized, and the PCR results were compared with those of DNA sequencing.

Results

In the optimized condition, the two polymorphisms could be clearly distinguished after one-step PCR and electrophoresis. The ABCB1 3435C/T and 2677G/T/A genotypes of the subjects were scanned, and allele-specific bands were successfully amplified by SSP-PCR, which were in full accordance with the results of sequencing.

Conclusion

As a fast, simple and inexpensive genotyping tool, the method would be practicable in large clinical studies on interindividual pharmacokinetics.
Cell Death Pathways in Response to Antitumor Therapy
Authors: Portugal José , Bataller Marc , Mansilla Sylvia
Published: February 2018

Failure to eliminate cancer cells that have been exposed to cytotoxic agents may contribute to the development of resistance to antitumor drugs. A widespread model in present day oncology is that antitumor therapy involves the triggering of tumor cells to undergo apoptosis, and cells that can avoid apoptosis will be resistant to such therapy. Apoptosis is a defined program of cell death that is markedly influenced by the fact that many routes leading to it are mutated or deregulated in human cancer. Mutations in the tumor suppressor protein p53, a common feature of many cancers, may decrease the sensitivity of cells to some antitumor agents. Moreover, it has been increasingly reported that antitumor therapy not only causes apoptosis, but other forms of cell death as well, such as mitotic catastrophe, necrosis and autophagy, or a permanent cell arrest with phenotype characteristics of senescence. Mitotic catastrophe is a form of cell death that results from abnormal mitosis, which does not seem to depend on wild-type p53. Sometimes mitotic catastrophe is used restrictively for faulty mitosis leading to cell death, which may occur via apoptosis or necrosis. We critically review herein how antitumor therapy may elicit the response of human cancers through different cell pathways leading to cell death.
Non-Pegylated Liposomal Doxorubicin in Combination with Cyclophosphamide or Docetaxel as First-Line Therapy in Metastatic Breast Cancer: A Retrospective Analysis
Authors: Livi Lorenzo , Meattini Icro , De Luca Cardillo Carla , Mangoni Monica , Greto Daniela , Petrucci Alessia , Rampini Andrea , Bruni Alessio , Galardi Alessandra , Cataliotti Luigi , Biti Giampaolo
Published: February 2018

Aims and background

Anthracyclines such as doxorubicin play a central role in the management of advanced breast cancer. Unfortunately, the clinical benefits of anthracyclines are limited by cardiotoxicity that can lead to the development of potentially fatal congestive heart failure. In order to limit anthracycline-related cardiotoxicity, liposomal formulations of doxorubicin have been developed. This retrospective analysis evaluated the experience obtained with non-pegylated liposomal doxorubicin as first-line therapy in 34 patients with metastatic breast cancer.

Methods

Patients received non-pegylated liposomal doxorubicin in combination with either cyclophosphamide (n = 14) or docetaxel (n = 20) for up to eight cycles, and efficacy and safety were assessed according to standard criteria.

Results

The overall response rate was 71%. The median progression-free survival was 8 months in patients receiving non-pegylated liposomal doxorubicin plus cyclophosphamide and 13.8 months in those receiving non-pegylated liposomal doxorubicin plus docetaxel (P = 0.2). The most commonly observed toxicities were grade 1–2 leucopenia, alopecia, nausea and vomiting; no grade 3–4 toxicities were observed. Overall, three patients (9%) experienced grade 1 cardiac toxicity.

Conclusions

Our results support the use of non-pegylated liposomal doxorubicin as an alternative to conventional doxorubicin formulations in combination regimens for the first-line therapy of metastatic breast cancer.
A Pilot Study of Irinotecan Combined with 5-Fluorouracil and Leucovorin for the Treatment of Chinese Patients with Locally Advanced and Metastatic Gastric Cancer
Authors: Li Qiu , Chen Jing , Zhao Xin , Yin Xude , Mei Kai , Zhou Chengya , Cai Xiaohong
Published: February 2018

Aims and background

The FOLFIRI regimen was evaluated for its anti-tumor activity and toxicity in Chinese patients with locally advanced and metastatic gastric cancer.

Methods and study design

Treatment consisted of irinotecan, 180 mg/m2 (90-min infusion), leucovorin, 200 mg/m2 (2-h infusion), followed by 5-fluorouracil, 400 mg/m2 (bolus), and then 5-fluorouracil, 600 mg/m2 (22-h continuous infusion) on days 1 and 2, every 14 days.

Results

Twenty-six patients, of whom 17 were pretreated, were included in the study. Partial response was observed in 9 patients (37.5%). The overall disease control rate was 83.3%. Median progression-free and overall survival was 6.8 and 11.2 months, respectively. Grade 3–4 neutropenia was observed in 6 patients (23.1%) and grade 2–3 diarrhea in 5 (19.2%). No treatment-related deaths occurred.

Conclusions

The results demonstrate that the FOLFIRI regimen is an active regimen with acceptable toxicity for Chinese patients with advanced and metastatic gastric cancer that merits further investigation in comparative trials.
Decreased Serum Levels of Carboxylesterase-2 in Patients with Ovarian Cancer
Authors: Cai Liying , Tang Xiaobo , Guo Lei , An Yuan , Wang Yuguang , Zheng Jianhua
Published: February 2018

Aims and background

Carboxylesterase-2 has been identified as the key enzyme in the metabolic activation of irinotecan, a topoisomerase I inhibitor commonly used in the treatment of many solid tumors. Previous studies have shown that carboxylesterase-2 is down-regulated in colorectal cancer following progression of the disease. However, very limited information is available on carboxylesterase-2 expression in ovarian cancer. The aim of the present study was to detect the serum level and the tissue expression of carboxylesterase-2 in human ovarian cancer patients at different stages of the disease.

Methods

Carboxylesterase-2 levels in the serum of ovarian cancer patients were investigated by western blot and ELISA and in the tumor mass of ovarian cancer patients by western blot.

Results

Both the serum carboxylesterase-2 level and the expression of carboxylesterase-2 in tumor tissues were significantly different among patients at different stages of the disease (n = 40). No positive correlation was found between the serum carboxylesterase-2 level and the cancer antigen 125 level (n = 40). Serum carboxylesterase-2 is more sensitive than cancer antigen 125 in detecting the early stage patient with ovarian cancer.

Conclusions

Our results indicate that serum carboxylesterase-2 level might be a potential marker in the diagnosis of the early stage ovarian cancer.
Chemopreventive Effect of a Novel Nutrient Mixture on Lung Tumorigenesis Induced by Urethane in Male A/J Mice
Authors: Roomi M Waheed , Roomi Nusrath W , Kalinovsky Tatiana , Rath Matthias , Niedzwiecki Aleksandra
Published: February 2018

Aims and background

Lung cancer, a leading cause of cancer death, is associated with exposure to inhalation carcinogens, most commonly those found in tobacco smoke. We investigated the in vivo effect of dietary supplementation with a nutrient mixture containing lysine, proline, arginine, ascorbic acid, green tea extract, N-acetyl cysteine, selenium, copper and manganese on the development of urethane-induced lung tumors in male A/J mice.

Methods

After one week of isolation, seven-week-old male A/J mice (n = 25) weighing 17–19 g were randomly divided into three groups: group A (n = 5), group B (n = 10), and group C (n = 10). Mice in groups B and C were each given a single intraperitoneal injection of urethane (1 mg/g body weight) in saline, whereas group A mice received an injection of saline alone. Groups A and B were fed a regular diet, whereas group C was fed the same diet supplemented with 0.5% nutrient mixture. After 20 weeks, mice were sacrificed, lungs were excised and weighed, and tumors were counted and processed for histology.

Results

Urethane-challenged mice developed tumors. However, the mean number of tumors and the mean lung weights in the mice on the supplemented diet were significantly reduced, by 49% (P <0.0001) and 18% (P = 0.0025), respectively, compared to mice on the control diet. We observed neither significant differences in body weight gains nor in diet consumption among the mice. Pulmonary lesions were morphologically similar for both the groups (adenomas), but lesions were smaller in the test group.

Conclusions

The results suggest that nutrient mixture has inhibitory potential on the development of mouse lung tumors induced by urethane
Tailgut Cyst, an Unusual Cause of Pseudomyxoma Peritonei
Authors: Zappa Luis , Godwin Thomas A , Sugarbaker Paul H
Published: February 2018

Background

Retrorectal hamartoma, also known as tailgut cyst, is a rare tumor that arises from remnants of the embryonic postanal gut. The tumor occurs in the retrorectal space and may undergo malignant degeneration.

Methods

The clinical information on a single patient with pseudomyxoma peritonei associated with a tailgut cyst was reviewed and a literature review of the subject performed.

Results

In this patient there was malignant degeneration of a tailgut cyst localized to the pelvis. Twenty months later a local recurrence in the pelvis and pseudomyxoma peritonei widely distributed in the abdomen were successfully treated by cytoreductive surgery and perioperative chemotherapy.

Conclusion

Tailgut cyst may, if resected with tumor spillage, result in pseudomyxoma peritonei. Our treatment – which has maintained a disease-free status for one year – was cytoreductive surgery plus perioperative chemotherapy.
Gemcitabine-Induced Supraventricular Tachycardia
Authors: Tayer-Shifman Oshrat E , Rottenberg Yakir , Shuvy Mony
Published: February 2018

The superior toxicity profile is one of the major reasons for the widespread use of gemcitabine in cancer treatment. Bone marrow suppression is the most common side effect, while non-hematological events are relatively infrequent. Cardiac toxicity is a rare complication and cardiac arrhythmia is even rarer. We report the case of a 67-year-old woman with metastatic breast cancer without a history of cardiac arrhythmia or ischemic heart disease who developed supraventricular tachycardia. The symptoms had started immediately after gemcitabine treatment. The arrhythmia responded poorly to common treatment and was eventually controlled by oral propranolol five days after admission. The present case suggests that supraventricular tachycardia may be triggered by gemcitabine even without underlying significant heart disease and may be resistant to conventional therapy.
Fulminant Liver Failure in a Patient Affected by Polycystic Liver Disease and Liver Metastases from Breast Carcinoma
Authors: Fadda Giovanni Maria , Santeufemia Davide Adriano , Cossu-Rocca Paolo , Bardino Gianfranco , Costantino Salvatore , Sanna Giovanni , Sarobba Maria Giuseppa , Farris Antonio
Published: February 2018

Background

Polycystic liver disease (PLD) is a rare, congenital, benign condition characterized by the presence of multiple bile-duct-derived epithelial cysts in the liver parenchyma. The disease is usually asymptomatic, but cyst growth can result in complications such as ascites, esophageal varices, jaundice and hepatic failure. The exact mechanism leading to cyst growth is unclear, but estrogenic stimulation and paracrine action of vascular endothelial growth factor (VEGF) are thought to play a role in the growth of cyst epithelium.

Case report

We report a case of acute liver failure in a young woman with PLD and liver metastases from breast carcinoma.

Results

No data are available in the literature about metastatic liver involvement in PLD patients affected by breast cancer. The prognosis of patients with liver metastases is generally poor but fulminant liver failure is a very rare occurrence. Estrogen stimulation seems to be a risk factor for breast cancer and severe PLD. In the reported case, the presence of either the cysts or the metastatic lesions may have resulted in more extensive liver damage.

Conclusions

The adoption of drugs selected in relation to their hepatic toxicity together with careful monitoring of liver function is warranted in the management of breast cancer patients affected by PLD, in order to reduce the risk of liver failure.
Strong Seasonality in the Diagnosis of Skin Melanoma in Italy: The Italian Network of Cancer Registries (AIRTUM) Study
Authors: Crocetti Emanuele , Guzzinati Stefano , Paci Eugenio , Falcini Fabio , Zanetti Roberto , Vercelli Marina , Rashid Ivan , De Lisi Vincenzo , Russo Antonio , Vitarelli Susanna , Ferretti Stefano , Mangone Lucia , Cesaraccio Rosaria , Tumino Rosario , Busco Susanna , Buzzoni Carlotta
Published: February 2018

Aim

To evaluate seasonality in the diagnosis of cutaneous melanoma in Italy.

Methods

A total of 16,284 invasive (and 1,235 in situ) cutaneous melanomas incident from 1978 to 2002 in 14 cancer registries belonging to the Italian Network of Cancer Registries (AIRTUM) was analyzed. We used the Walter and Elwood test to evaluate seasonality. The monthly distribution of diagnosis was evaluated for sex, skin site, melanoma morphology and period of diagnosis.

Results

The overall monthly diagnosis of invasive melanoma showed a statistically significant excess around the month of June. The same pattern was present for males and females, across age-groups and periods of time. All skin sites showed a cycling trend, melanoma of the head and neck peaked around April, all the others peaked around June. As regards morphologic types, a cyclic trend was evident for superficial-spreading melanomas (peak around July), for not-specified melanomas (June) and for other histotypes (June). Diagnosis of in situ melanoma peaked in September.

Conclusions

The present study showed that also in Italy melanoma diagnosis has a seasonal trend, with the peak in early summer. It seemed that summer UV exposure, acting both as a late promoter of malignant melanoma development and also increasing the visibility of pigmented skin lesion, may be relevant to explain such a peak.
Sentinel Lymph Node Biopsy in Patients with Pure and High-Risk Ductal Carcinoma in Situ of the Breast
Authors: D'eredità Giovanni , Giardina Carmela , Napoli Anna , Ingravallo Giuseppe , Leopoldo Troilo Vito , Fischetti Fernando , Berardi Tommaso
Published: February 2018

Aims and Background

The role of sentinel lymph node biopsy in patients initially diagnosed with ductal carcinoma in situ resides in determining the predictors of invasive disease. The aim of the present study was to examine the incidence of sentinel lymph node metastases in a selected group of patients, with characteristics of high-risk ductal carcinoma in situ, in order to determine the clinical usefulness of sentinel lymph node biopsy.

Methods

A total of 90 patients with a biopsy diagnosis of ductal carcinoma in situ were treated. Fifty-two patients with high-risk ductal carcinoma in situ had sentinel lymph node biopsy. The following characteristics of the primary tumor were considered as indicative of a risk of invasive disease: presence of palpable mass, mammographic mass, multicentric disease that required mastectomy, and histologically high nuclear grade or non-high nuclear grade with necrosis. Subdermal injections of 99mTc-labeled human albumin and subareolar injection ofblue dye were used for sentinel lymph node identification. All sentinel nodes were sectioned serially and stained with hematoxylin and eosin. Immunohistochemical analysis was performed using a cytokeratin monoclonal antibody.

Results

A positive sentinel lymph node was found in only one patient (1.9%). The patient had a double lesion, and core-needle biopsy showed an atypical ductal hyperplasia and a intermediate degree of ductal carcinoma in situ. At pathologic review of the specimen, no invasive aspect was detected.

Conclusions

The results of our study indicate that sentinel lymph node metastasis in pure ductal carcinoma in situ is extremely uncommon. We therefore suggest that sentinel lymph node biopsy might be indicated for patients with ductal carcinoma in situ detected as a palpable mass or as large extensive microcalcifications, as well as for patients who are undergoing mastectomy, especially with immediate reconstruction.
DNA/RNA Markers for Colorectal Cancer Risk in Preserved Stool Specimens: A Pilot Study
Authors: Kato Ikuko , Badsha Kawsar Z , Land Susan , Nechvatal Jordan M , Matherly Larry H , Tarca Adi L , Majumdar Adhip P , Basson Marc D , Ram Jeffrey L
Published: February 2018

Aims and Background

Exfoliated cells in human stool offer excellent opportunities to non-invasively detect molecular markers associated with colorectal tumorigenesis, and to evaluate the effects of exposures to exogenous and endogenous carcinogenic or chemopreventive substances. This pilot study investigated the feasibility of determining DNA methylation and RNA expression simultaneously in stool specimens treated with a single type of nucleic acid preservatives.

Methods

Stool specimens from 56 volunteers that were preserved up to a week with RNAlater were used in this study. Bisulfite sequencing was used to determine methylation at 27 CpG loci on the estrogen receptor 1 ( ESR1) promoter. Taqman assay was used for quantitative reverse transcription polymerase chain reactions to measure cyclooxygenase 2 ( COX2) and epidermal growth factor receptor ( EGFR) mRNA expression. Subjects’ basic demographic and other selected risk factors for colorectal cancer were captured through questionnaires and correlated with the levels of these markers.

Results

Less than 10% of the samples failed in individual assays. Overall, 24.0% of the CpG loci on the ESR1 promoter were methylated. COX2 expression and alcohol use were positively correlated; an inverse association was present between EGFR expression and cigarette smoking; and subjects using anti-diabetic medication had higher ESR1 methylation. In addition, higher EGFR expression levels were marginally associated with history of polyps and family history of colorectal cancer.

Conclusions

The present study demonstrates that simultaneous analyses for DNA and RNA markers are feasible in stool samples treated with a single type of nucleotide preservatives. Among several associations observed, the association between EGFR expression and polyps deserves further investigation as a potential target for colorectal cancer screening. Larger studies are warranted to confirm some of our observations.
Distribution of 4-Hydroxynonenal-Protein Conjugates as a Marker of Lipid Peroxidation and Parameter of Malignancy in Astrocytic and Ependymal Tumors of the Brain
Authors: Juric-Sekhar Gordana , Zarkovic Kamelija , Waeg Georg , Cipak Ana , Zarkovic Neven
Published: February 2018

Aims and Background

Lipid peroxidation (LPO) is an autocatalytic process caused by oxidative stress. It results in the production of 4-hydroxynonenal (HNE), which plays a crucial role in hypoxic brain injury, neuronal degeneration and apoptosis. The aim of this study was to evaluate the expression of HNE in 120 astrocytic and 40 ependymal tumors in relation to tumor type, grade of malignancy, angiogenesis, and presence of necrosis and apoptosis.

Methods

Immunohistochemical staining was performed using a monoclonal antibody for the detection of HNE-modified proteins.

Results

HNE-protein adducts were found in all tumors. The incidence of HNE-im-munopositive tumor cells increased with increasing grades of malignancy. Significantly higher HNE expression was found in tumor cells of glioblastomas multiforme than in cells of pilocytic astrocytomas ( P <0.005), and in anaplastic ependymomas than in benign ependymomas ( P <0.01). HNE-immunopositive tumor cells were distributed more diffusely than in perivascular locations ( P <0.05). Pronounced HNE-protein adducts were detected in mitotic, necrotic, and apoptotic cells. HNE was expressed in the endothelium of almost all tumor vessels, but its expression in the walls of the vessels was significantly higher in diffuse and anaplastic astrocytomas than in pilocytic astrocytomas and glioblastomas multiforme ( P <0.05). The number of microvessels containing HNE in their endothelium and walls was significantly associated with the grade of malignancy in both astrocytic ( P <0.001) and ependymal tumors ( P <0.05), although microvessels in pilocytic astrocytomas were significantly more numerous ( P <0.05) than in diffuse astrocytomas.

Conclusions

LPO seems to be a common pathological process in astrocytic and ependymal glial tumors, proportional to the level of malignancy and neovascularization. Therefore, HNE might be involved in the damage of brain cells and the induction of malignancy.
Fibronectin Promotes Tyrosine Phosphorylation of Paxillin and Cell Invasiveness in the Gastric Cancer Cell Line AGS
Authors: Li Dan , Ding Jian , Wang Xiaozhong , Wang Chengdang , Wu Ting
Published: February 2018

Aims and Background

Paxillin is a central protein within the focal adhesion and serves as a critical transducer of signals from fibronectin. Although abnormal expression of fibronectin and paxillin is often observed during the development of human malignancies, the relationship between paxillin and cell invasion in gastric cancer is still unclear. The current study was designed to investigate the potential role and mechanisms of fibronectin in tyrosine phosphorylation of paxillin and in the invasiveness of gastric cancer cells.

Methods

Expression of paxillin in human gastric cancer samples was examined by immunohistochemical staining. A gastric cancer cell line, AGS, was stimulated by fibronectin with gradient concentrations, and expression of paxillin and phosphorylation of paxillin tyrosine 118 (tyr118) was detected by immunoprecipitation and Western blotting. The invasiveness of AGS cells was measured by the modified Boyden chamber assay. Small interfering RNA (siRNA) targeting paxillin was used to establish the role of paxillin (tyr118) in the process of cell invasion enhanced by fibronectin. siRNA targeting focal adhesion kinase (FAK) was used to verify the effect of FAK tyrosine 397 (tyr397) on phosphorylation of paxillin(tyr118).

Results

Positivity for paxillin staining in human gastric cancer was associated with tumor stage. AGS cell showed dose dependence on fibronectin for invasiveness and phosphorylation of paxillin (tyr118). Invasiveness and phosphorylation of paxillin(tyr118) in AGS cells reached their peak when the concentration of fibronectin reached 100 nmol/L. siRNA targeting paxillin decreased the phosphorylation of paxillin(tyr118) and the invasiveness of AGS cells significantly as compared with controls. Blockage of FAK(tyr397) can inhibit phosphorylation of paxillin(tyr118) stimulated by fibronectin.

Conclusions

Fibronectin promotes paxillin(tyr118) phosphorylation and invasiveness of AGS cells. Paxillin silencing by RNA interference inhibits the cell invasiveness stimulated by fibronectin. Paxillin is a key factor in the fibronectin-stimulated invasiveness of AGS cells.
Inhibition of HER2/estrogen Receptor Cross-Talk, Probable Relation to Prolonged Remission of Stage IV Breast Cancer: A Case Report
Authors: Tisman Glenn
Published: February 2018

Metastatic breast cancer to the liver is considered incurable. Though many patients with liver metastases may enjoy response to chemo-, immuno- and hormonal therapy, those so inflicted rarely remain disease-free from the time of diagnosis for longer than 6-11 months. New laboratory and clinical research identified that cross-talk between activation of the epidermal growth factor family of tyrosine kinase transduction pathways (EGF/HER2) and estrogen receptor (ER) activation plays a role in resistance to hormonal therapy.

A 59-year-old woman with a 4.5-cm invasive ductal, ER-positive/PR-negative, grade III adenocarcinoma of the breast was treated with mastectomy. Staging revealed biopsy-proven liver metastases. Surgery was immediately followed with vinorelbine, trastuzumab, tamoxifen and exemestane. The patient underwent a bone scan and PET/CT documented complete remission. She has remained in complete remission for 7 years. It is proposed that a possible mechanism for prolonged remission of stage IV breast cancer in this patient may be related to suppression of EGF/HER2 by trastuzumab, thus inhibiting cross-talk-associated tamoxifen/estrogen withdrawal resistance.