bluuebunny/crossref_metadata_2025 huggingface dataset:
Attenuated Salmonella Typhimurium Carrying TRAIL and VP3 Genes Inhibits the Growth of Gastric Cancer Cells in Vitro and in Vivo
Authors: Cao Hong-Dan , Yang Yin-Xue , Lü Lin , Liu Shao-Ning , Wang Pi-Long , Tao Xiao-Hong , Wang Li-Juan , Xiang Ting-Xiu
Published: February 2018

Background

Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand (TRAIL) and apoptin (VP3) of chicken anemia virus can selectively induce apoptosis in human tumor cell lines by two different pathways. Salmonella not only delivers functional genes to mammalian cells but also possesses antitumor activity and therefore could be adopted as a novel vector for anticancer therapy.

Materials and methods

TRAIL and VP3 genes were cloned into a pBudCE4.1 vector and delivered by attenuated Salmonella typhimurium into gastric cancer cells, and their expression and antitumor effects in nude mice were monitored by Western blot, fluorescence microscopy, MTT assay, TUNEL staining, and immunohistochemistry.

Results

pBud-VP3 and pBud-TRAIL-VP3 plasmids were constructed to express TRAIL and apoptin in gastric cancer cells, leading to inhibition of cancer cell proliferation after 48 hours (P <0.05). TRAIL and VP3 genes in pBudCE4.1 vector were also successfully delivered by attenuated S. typhimurium into gastric cancer cells in vivo, in which both TRAIL and apoptin were expressed. In vivo data indicated that S. typhimurium carring pBud-TRAIL-VP3 induced significant cell growth inhibition and tumor regression (P <0.05). Moreover, expression of TRAIL and apoptin increased the expression of caspase-3 and caspase-9, resulting in enhanced apoptosis.

Conclusion

Delivery of TRAIL and VP3 genes by attenuated S. typhimurium can significantly inhibit the growth of gastric cancer cells in vitro and in vivo.
Overexpression of Smac/DIABLO in Hep-2 Cell Line: Possible Role in Potentiating the Sensitivity of Chemotherapeutic Drugs
Authors: Lu Sumei , Xu Wei , Fan Zhaomin , Liu Wenwen , Li Jianfeng , Wang Haibo
Published: February 2018

Aims and background

The major obstacles for tumor chemotherapy are drug resistance and/or adverse effects on the host. In the present study we investigated the role of the second mitochondria-derived activator of caspase (Smac/DIABLO) in the action of cisplatin (DDP), 5-fluorouracil (5-FU), and the combination of both in Hep-2 cells.

Methods and study design

Hep-2 laryngeal carcinoma cells exposed to DDP, 5-FU and the combination of both were investigated. Cell viability was determined by MTT assay. Apoptosis was measured by Ho.33342 and PI double staining and flow cytometry. The expression of Smac/DIABLO at the mRNA and protein level was assayed by RT-PCR and Western blotting.

Results

DDP, 5-FU and the combination of both drugs reduced the cell survival rates in a concentration- and time-dependent manner. The drug combination not only exerted a stronger inhibitory effect, but also at a lower concentration compared with the single drugs. Apoptosis was concomitant in a caspase-dependent manner. The expression of Smac/DIABLO increased significantly at both mRNA and protein levels after cell exposure to the combination compared with single drugs.

Conclusions

Smac/DIABLO plays a pivotal role in attaining a synergistic effect in Hep-2 cells in response to this combined strategy.
Optimizing Craniospinal Radiotherapy Delivery in a Pediatric Patient Affected by Supratentorial PNET: A Case Report
Authors: Mascarin Maurizio , Drigo Annalisa , Dassie Andrea , Gigante Marco , Franchin Giovanni , Sartor Giovanna , Trovò Mauro G
Published: February 2018

New advances in radiation therapy for children allow increased conformability and reduced doses to non-target tissues. We report our experience in treating a 4-year-old child with craniospinal tomotherapy after surgery of the primary tumor, a supratentorial primitive neuroectodermal tumor. The tomotherapy plan was compared with conventional craniospinal irradiation, 3D conformal radiation therapy, and intensity-modulated radiation therapy plans. The possible disadvantages of tomotherapy related to the radiation dose to organs at risk, treatment planning, and anesthesia should be carefully considered as the use of the technique is not suggested in a general manner, but selectively, in critical pediatric radiotherapy cases.
Mesenteric Cyst: Report of a Case Resulting in Pseudomyxoma Peritonei
Authors: Zappa Luis , Sugarbaker Paul H
Published: February 2018

Background

A mesenteric cyst may have an embryonic, traumatic, neoplastic or infectious origin. In rare cases mesenteric cysts may contain neoplastic epithelium. A mesenteric cyst has not previously been recorded as the cause of pseudomyxoma peritonei.

Methods

A patient who developed widespread mucinous intraperitoneal tumor as a result of a ruptured mesenteric cyst is reported. A literature review of the clinical features, diagnosis, treatment, and prognosis of the mesenteric cyst is presented.

Results

This patient was treated with cytoreductive surgery and perioperative intraperitoneal chemotherapy. Her recovery was uneventful and she remains well two years after treatment.

Conclusion

Mesenteric cyst is a rare cause of pseudomyxoma peritonei. The definite treatment of a ruptured neoplastic mesenteric cyst can, by analogy, be compared to the treatment for pseudomyxoma peritonei of appendiceal origin. The results of cytoreductive surgery with perioperative intraperitoneal chemotherapy are expected to be good.
A Rare Case of Primary Small Bowel Adenocarcinoma with Intussusception
Authors: Caruso Stefano , Marrelli Daniele , Pedrazzani Corrado , Neri Alessandro , Mazzei Maria Antonietta , Onorati Monica , Corso Giovanni , Cerullo Guido , Roviello Franco
Published: February 2018

Other than in childhood, intussusception is unusual and nearly always caused by a structural and well demonstrable lesion. In contrast with the colon tract, the incidence of primary malignancies in the small bowel is very low. We report the case of a 51-year-old man presenting with jejunal intussusception due to a primary adenocarcinoma. To our knowledge, only a few similar cases have been reported in the literature to date. The patient was referred to our division for bowel obstruction. A CT scan showed a jejunal intussusception and surgical exploration was hence considered. At laparotomy, jejunal intussusception located just after the ligament of Treitz due to a polypoid lesion was confirmed and resection of the first jejunal loop was carried out. Histological examination of the specimen resulted in a diagnosis of a primary adenocarcinoma of the small bowel. In adult intestinal intussusception, resection without reduction is considered the optimal management if an underlying primary malignancy cannot be excluded.
CD138-Positive Plasmacytoid Urothelial Carcinoma of Urinary Bladder with Focal Micropapillary Features
Authors: Demirovic Alma , Marusic Zlatko , Lenicek Tanja , Spajic Borislav , Balicevic Drinko , Tomas Davor , Kruslin Bozo
Published: February 2018

Both the plasmacytoid and micropapillary types of urothelial carcinoma of the urinary bladder are uncommon, distinct clinical and pathological findings. To date, several reports in the English medical literature have been published on either of these variants. CD138 is commonly used as a marker for tumors of plasma cell origin. However, few authors have described positive immunoreactivity of plasmacytoid cells in urothelial carcinoma. Mixed histological differentiation is thought to be a phenotype of locally aggressive and advanced urothelial carcinoma. Therefore, a precise histopathological diagnosis should be made and awareness of all the entities is crucial. We report a case of CD138-positive plasmacytoid urothelial carcinoma of the bladder with focal micropapillary features. To our knowledge this is the first case of these two rare subtypes of urothelial carcinoma combined in a single cystectomy specimen.
Is there a Specific Magnetic Resonance Phenotype Characteristic of Hereditary Breast Cancer?
Authors: Trecate Giovanna , Manoukian Siranuosh , Suman Laura , Vergnaghi Daniele , Marchesini Monica , Agresti Roberto , Ferraris Cristina , Peissel Bernard , Scaramuzza Davide , Bergonzi Silvana
Published: February 2018

Aims and background

The aim of the study was to investigate the growth rate of inherited breast cancer, to analyze its T2 signal intensity besides kinetic and morphologic aspects, and to verify whether there is any correlation between magnetic resonance imaging phenotype and BRCA status.

Methods

Between June 2000 and September 2009, we enrolled 227 women at high genetic risk for breast cancer in a surveillance program, within a multicenter project of the Istituto Superiore di Sanità (Rome).

Results

Thirty-four cancers were detected among 31 subjects. One patient refused magnetic resonance imaging because of claustrophobia. Compared with sporadic disease, hereditary cancer showed some differences, in terms of biologic attitude and semeiotic patterns. These differences were mainly registered for magnetic resonance imaging, where the most frequent radiological variant was represented by the very high T2 signal intensity (73%). Moreover, the size of 8 of the neoplasms showed a significant increase in less than one year, 5 of them in less than 6 months. Six lesions were in BRCA1 patients and the remaining in BRCA2. Furthermore, cancers with a high growth rate also demonstrated a significant increment in T2 signal intensity.

Conclusions

Our results confirmed the high growth rate within BRCA-related breast cancers, especially for BRCA1 mutation carriers. In our experience, we found a specific imaging phenotype, represented by the high T2 signal intensity of hereditary breast cancer. To our knowledge, this is the first report that points out this new semeiotic parameter, which is usually typical of benign lesions. Considering the correlation between high growth rate and high T2 signal intensity, the former seems to be related to the absence of induction of a desmoplastic reaction that could somehow restrict cancer growth.
Metastatic Breast Cancer Shows Different Immunohistochemical Phenotype According to Metastatic Site
Authors: Koo Ja Seung , Jung Woohee , Jeong Joon
Published: February 2018

Aims and background

The study was performed to assess the status of immunohistochemical markers in primary and metastatic breast cancer and to determine the organ-specific characteristics of metastatic breast cancer.

Methods

Samples from 13 cases of paired primary and metastatic breast cancer and 34 cases of metastatic breast cancer were included.

Results

In the analysis of 13 cases of paired primary and metastatic breast cancer, estrogen receptor and progesterone receptor loss were noted in 1 (7.7%) case each. Androgen receptor loss and gain was noted in 2 (15.4%) cases, respectively. HER-2 showed 100% concordance with primary and metastatic tumors. C-kit was demonstrated in only 2 (15.4%) cases of metastatic breast cancer. In the analysis of 34 cases of metastatic breast cancer, when classified into triple-negative type (ER-, PR-, and HER-2-), HER-2+ type, and ER+ or PR+/HER-2- type according to immunohistochemical stain results, HER-2 type (66.7%) in brain metastasis and ER+ or PR+/HER-2- type (75.0%) in liver metastasis were predominant. Bone metastasis was composed of triple negative type (44.4%) and ER+ or PR+/HER-2- type (55.6%), and lung metastasis showed all of three subtypes in similar proportions.

Conclusions

Metastatic breast cancer shows different immunohistochemical phenotypes according to metastatic site (P = 0.048).
Glycosyl-Phosphatidylinositol-Anchored Interleukin-2 Expressed on Tumor-Derived Exosomes Induces Antitumor Immune Response in Vitro
Authors: Zhang Jiamo , Zhang Yao , Luo Chunli , Xia Yuguo , Chen Honglin , Wu Xiaohou
Published: February 2018

Aims and background

Tumor-derived exosomes (TEXs) have been considered as a new kind of cancer vaccine, but the antitumor effects are not satisfactory. In order to improve the efficacy of TEXs, we investigated whether exosomes derived from glycosyl-phosphatidylinositol-anchored interleukin 2 (GPI-IL-2) gene-modified bladder cancer cells can increase the antitumor effects.

Methods and study design

We transfected melanoma antigen-1 (MAGE-1)-expressing T24 tumor cells with a plasmid encoding GPI-IL-2 and prepared the TEXs. Exosomes expressing GPI-IL-2 were characterized by electron microscope and Western blot analysis.

Results

IL-2 was present on the cell surface in the GPI-anchored form as demonstrated by fluorescent microscope and ELISA analyses. Exosomes expressing GPI-IL-2 naturally contained bioactive GPI-IL-2 and tumor-associated antigen MAGE-1. Moreover, exosomes expressing GPI-IL-2-pulsed dendritic cells could induce the proliferation of T cells and the antigen-specific cytotoxic T-lymphocyte immune response more efficiently.

Conclusions

GPI-IL-2 gene-modified tumor cells can make the TEXs contain GPI-IL-2, resulting in increased antitumor effects. Our study provided a feasible approach for exosome-based tumor immunotherapy.
Successful Treatment with the Fully Human Antibody Panitumumab after a Severe Infusion Reaction with Cetuximab
Authors: Brugger Wolfram
Published: February 2018

Aims and background

There are only limited data on the safety and efficacy of panitumumab in patients who experienced severe infusion reactions during cetuximab antibody therapy.

Case report

We report the case of a 69-year-old woman with chemotherapy-refractory metastatic colorectal cancer who received single-agent cetuximab treatment but experienced a severe reaction during the first infusion, despite premedication with corticosteroids/antihistamines. Cetuximab was discontinued and treatment with panitumumab initiated approximately 14 days later (without premedication); no infusion reactions occurred and there was a rapid improvement in her general condition. She experienced a partial response that was sustained for 7 months before progression.

Conclusions

This case supports the use of panitumumab in patients with chemotherapy-refractory metastatic colorectal cancer and suggests that panitumumab may be used in some patients with prior infusion reactions to cetuximab.
Prolonged Response to Cytoreductive Surgery and Sunitinib in an Elderly Patient with Synchronous Multiple Metastases from Renal Cell Carcinoma
Authors: Locatelli Maria Cristina , Miedico Aurora , D'Antona Adelaide , Longo Giovanni , Maggioni Matteo , Maggioni Augusto , Tombolini Pietro , Tabiadon Donata
Published: February 2018

One third of patients with renal cell cancer have metastatic disease at diagnosis. Until now the outcome of these patients has been poor due to the variable natural history of the disease and the lack of effective therapy. Multitargeted therapy of advanced renal cell cancer appears to be a better option than immunotherapy. We report the case of an elderly patient with skin, lung, bone and brain metastases and widespread intraabdominal disease treated with cytoreductive surgery and sunitinib, resulting in a prolonged response.
EGFR Polysomy in Squamous Cell Carcinoma of the Thyroid. Report of Two Cases and Review of the Literature
Authors: Bonetti Luca Reggiani , Lupi Massimo , Trani Margherita , Trani Nicoletta , Sartori Giuliana , Schirosi Laura , Bettelli Stefania , Zanelli Giuliana , Maccio Livia , Maiorana Antonio
Published: February 2018

Aims and background

Primary squamous cell carcinoma of the thyroid gland (PSCCT) is an uncommon malignancy characterized by a poor prognosis. A radical surgical approach combined with radiotherapy or chemotherapy is the generally accepted treatment for this tumor. The epidermal growth factor receptor (EGFR) is a transmembrane tyrosine kinase receptor modulating the cell proliferation and biological progression of many human epithelial tumors. The EGFR overexpression in PSCCT suggests an additional therapeutic option for the treatment of this tumor.

Methods and study design

The clinicopathological features and immunohistochemical profiles of two cases of primary squamous cell carcinoma of the thyroid in a 66-year-old and an 83-year-old woman are presented. EGFR status was valued in both cases.

Results

Overexpression of EGFR protein was detected in 50% and 75% of the tumor cell membranes. EGRF gene polysomy was detected in both tumors.

Conclusions

Pharmaceuticals targeting EGFR may help to provide the rationale for an additional, novel therapeutic option for this rare tumor, especially when other therapeutic options have been exhausted.
Past, Present and Future of the Cervical Cancer Screening in Latvia
Authors:   on behalf of the EUROCHIP Working Group, Viberga Ilze , Engele Ludmila , Baili Paolo
Published: February 2018

Objective

The present descriptive study summarizes the historical activity on cervical cancer screening in Latvia, assesses the current screening situation, and defines the existing and expected obstacles and problems for the implementation of a proper organized population-based cervical cancer screening program in Latvia.

Material and methods

Available data on cervical cancer burden were collected from Latvian cancer registry. Availability of trained medical staff and laboratory systems were obtained through the Latvian Association of Cytologists and the Health Compulsory Insurance State Agency of Latvia (HCISA).

Results

Cervical cancer incidence in Latvia is increasing since 1989 when the compulsory preventive gynecologic examinations were stopped. Cervical opportunistic screening program in Latvia should be performed by GPs. But only 30 out of 1470 GPs provide gynecological care for their patients while, out of 484 certified gynecology practitioners, 35 had direct contractual relationship with the HCISA while 398 had only an indirect contractual relationship with the Agency. Moreover, in Latvia, there are about 29 laboratory specialists employed with cytological testing with an average age of 57 years: 13 of them have already passed the retirement limit.

Conclusions

Traditionally in Latvia, most women request gynecological services for preventive and health promotion reasons or in the case of having a gynecological disease. So the overloaded general practitioners and the lack of involvement of gynecologists are one of the main obstacles to solve for implementing an organized screening program in Latvia. Moreover insufficient availability of quality-assured services and resources for cytology testing and other services of the program, and for monitoring and evaluating the whole program, must be considered in the implementation of a comprehensive screening plan.
Outcomes of Radiation Therapy for T1 Glottic Carcinoma from an Italian Regional Series with Doses Ranging from 60 to 66 Gy
Authors: Manzo Roberto , Ravo Vincenzo , Murino Paola , Morra Anna , Panetti Giuseppe , Laudati Antonio , Prisco Agnese , Panelli Giancarlo , Muto Paolo
Published: February 2018

Aims and background

Radiotherapy has remarkable success rates for the cure of patients affected by glottic carcinoma; local control rates are similar to surgery with lower morbidity and better functional results. Our aim was to determine local-regional control rates, overall survival, second cancer incidence, acute-late toxicity and prognostic factors in our series of T1 glottic cancer patients with radiation doses of 60 to 66 Gy. Functional results were not sufficient for statistical analysis.

Methods and study design

A retrospective study was carried out of all T1N0 glottic carcinomas treated with radiation therapy between 1996 and 2006. To be eligible, patients had to have newly diagnosed cancer and had to be treated with a curative intent by radiation therapy alone. Ninety-eight patients satisfied the eligibility requirements: 85 patients had T1a disease; 13 patients were staged as T1b. Treatment was performed for all cases with a 6 megavoltage linear accelerator. The total dose prescribed varied from 60 to 66 Gy: 2 Gy/fraction, 1 fraction/day, 5 fractions/week. During treatment, a weekly clinical evaluation was performed; endoscopic examination was performed once every two weeks. After the treatment, a clinical, endoscopic and radiological follow-up was performed every three months for the first two years, every 6 months till the fifth year, and then once a year.

Results

With a median follow-up of 41.5 months (range, 10-132; mean, 56.8), we registered 12 cases of local failures; 8 of them were successfully treated with salvage surgery (median time to relapse, 3–48 months). The local relapse rate was 12.2%, and disease-specific survival, taking into account salvage surgery, was 6%. Thirty-four deaths were registered: 2 for local progression, 2 for distant metastasis, 4 for a new primary cancer, and 26 for non-neoplastic causes. Five- and 10-year overall survival were respectively 85.8% and 69.4%. Four cases of lung cancer were detected in the upper aerodigestive tract in our series. In terms of acute-late toxicity, no grade 3-4 dermatitis, dysphagia or hoarseness occurred. Mild dermatitis and arythenoid edema were the most common causes of toxicity. Only one patient did not complete the treatment (60 Gy instead of the planned 66 Gy).

Conclusions

Our series confirmed the primary role of radiation therapy for the cure of T1N0 glottic cancer. Outcomes were good in terms of local-regional control as well as overall toxicity. Radiation therapy can be offered to T1 glottic cancer patients as a valid alternative to surgery, with high rates of functional preservation.
Influence of Surgical Trauma on Neopterin Concentrations in Gastric Carcinoma Patients
Authors: Engin Ayse Basak , Engin Atilla , Sepici-Dincel Aylin
Published: February 2018

Aims and background

Impairment of immune surveillance in the immediate postoperative period may accelerate the growth of tumor cells that remain despite radical resection in advanced cases. The present study was undertaken to evaluate the impact of major surgical trauma on host cellular immunity of gastric carcinoma cases.

Methods and study design

Sixty-eight consecutive patients with gastric carcinoma were divided into three subgroups according to the classification of the American Joint Committee on Cancer Staging, and they underwent surgery with a curative intent. Thirty-eight cancer-free patients served as controls, and they underwent surgical management for benign diseases. Physiological and Operative Severity Score for the enUmeration of Mortality and Morbidity (POSSUM) risk adjustment system was used to estimate the operative and physiological scores of patients. Plasma cortisol, serum interleukin-6 and high-sensitive C-reactive protein levels were determined in order to assess the severity of trauma-related inflammatory response. The frequency of increased neopterin concentrations of cancer patients was estimated by comparison with the average values of controls.

Results

Response of interleukin-6 to surgery was closely related with the postoperative cortisol of cancer patients, but not correlated with neopterin and high-sensitive C-reactive protein levels. Although the extent of tumor invasion might have gradually decreased the macrophage response to surgical trauma, the overall increase in postoperative neopterin levels of cancer cases was highly significant. However, maximal frequency of increased neopterin concentration was obtained in advanced group.

Conclusions

Macrophages might recognize the traumatic challenges in every stage of gastric cancer. Increasing individual neopterin concentration was not solely specific for tumor growth, but it was partially predictive of immune competence even in advanced cases.
Long-term Survival of Metastatic Melanoma to the Ileum with Evidence of Primary Cutaneous Disease after 15 years of follow-up: A Case Report
Authors: Sciacca Venerina , Ciorra A Alida , Di Fonzo Concetta , Rossi Rosalinda , Pistillucci Giorgio , Lugini Antonio , D'Aprile Modesto
Published: February 2018

The small bowel is the most common site of gastrointestinal metastasis from cutaneous melanoma. Malignant melanoma has a poor prognosis, especially if distant metastases appear. Although rare primary melanoma of the small bowel has been described, more frequently these lesions originate from unknown cutaneous melanoma. Here we report the case of a 58-year-old man with a diagnosis of melanoma of the ileum without evidence of primary cutaneous disease. After 15 years, during the clinical and radiological follow-up, a cutaneous melanoma in the left parietal side of the scalp, probably corresponding to the primary lesion with abdominal node metastasis, was diagnosed. After 6 months of chemotherapy with fotemustine, the patient showed a complete response. At present, he is still alive 18 years after the diagnosis of intestinal metastasis.
Combination Effect of Cetuximab with Radiation in Colorectal Cancer Cells
Authors: Shin Hye Kyung , Kim Mi-Sook , Lee Jin Kyung , Lee Seung-Sook , Ji Young Hoon , Kim Jong-Il , Jeong Jae-Hoon
Published: February 2018

Aims and background

Colorectal cancer (CRC) is one of the commonest malignant disorders and frequently associated with high expression of epidermal growth factor receptor (EGFR), resulting in advanced disease and a poor prognosis. In this study, we investigated the radiosensitizing effects of the selective EGFR inhibitor cetuximab in human CRC cell lines.

Methods

Four human CRC cell lines, CaCo-2, HCT-8, LoVo, and WiDr, were treated with cetuximab and/or radiation. The effects on cell proliferation and viability were measured by MTT and annexin-V staining, and clonogenic survival assay. The in vivo effect on the growth of CRC xenografts was assessed in athymic nude mice.

Results

Cetuximab in combination with radiation significantly inhibited the in vitro proliferation of CRC cells, with a concomitant increase in cell death, except in WiDr cells. Clonogenic survival assay confirmed that cetuximab worked as a radiosensitizer in three cetuximab-sensitivie CRC cells. However, no correlations were found between the radiosensitivity and EGFR expression level or mutation status of EGFR signaling molecules. In nude mice bearing CRC cell xenografts, cetuximab plus radiation significantly inhibited the tumor growth over either agent alone. Interestingly, the WiDr xenograft was also sensitive to cetuximab and/or radiation in vivo, suggesting host-mediated effects of cetuximab.

Conclusions

Cetuximab enhanced the radiosensitivity of CRC cells in vitro and efficiently inhibited xenograft tumor growth. This study provided a rationale for the clinical application of the selective EGFR inhibitor cetuximab in combination with radiation in CRC. Free full text available at www.tumorionline.it
Promoter methylation of p16, Runx3, DAPK and CHFR genes is frequent in gastric carcinoma
Authors: Hu Shi-Lian , Kong Xiang-Yong , Cheng Zhao-Dong , Sun Yu-Bei , Shen Gan , Xu Wei-Ping , Wu Lei , Xu Xiu-Cai , Jiang Xiao-Dong , Huang Da-Bing
Published: February 2018

Aims and background

Transcriptional silencing induced by hypermethylation of CpG islands in the promoter regions of genes is believed to be an important mechanism of carcinogenesis in human cancers including gastric cancer. A number of reports on methylation of various genes in gastric cancer have been published, but most of these studies focused on cancer tissues or only a single gene. In this study, we determined the promoter hypermethylation status and mRNA expression of 4 genes: p16, Runx3, DAPK and CHFR.

Methods

Methylation-specific polymerase chain reaction (MSP) was used to determine the methylation status of p16, Runx3, DAPK and CHFR gene promoters in cancer and adjacent normal gastric mucosa specimens from 70 patients with gastric cancer, as well as normal gastric biopsy samples from 30 people without cancer serving as controls. In addition, the mRNA expression of p16, Runx3, DAPK and CHFR was investigated in 34 gastric cancer patients by RT-PCR. Bisulfite DNA sequence analysis was applied to check the positive samples detected by MSP.

Results

When carcinoma specimens were compared with adjacent normal gastric mucosa samples, a significant increase in promoter methylation of p16, Runx3, DAPK and CHFR was observed, while all 30 histologically normal gastric specimens were methylation free for all 4 genes. The methylation rate of the 4 genes increased from normal stomach tissue to tumor-adjacent gastric mucosa to gastric cancer tissue. Concurrent methylation in 2 or more genes was found in 22.9% of tumor-adjacent normal gastric mucosa and 75.7% of cancer tissues. No correlation was found between hypermethylation and other clinicopathological parameters such as sex, age, and tumor location. However, the frequency of DAPK and CHFR methylation in cancer tissues was significantly associated with the extent of differentiation and lymph node metastasis (P <0.05) and the frequency of Runx3 methylation was significantly associated with tumor size (P <0.05). Weak expression and loss of expression of the 4 genes was observed in cancer tissues and was significantly associated with promoter hypermethylation (P <0.05).

Conclusions

Promoter hypermethylation of p16, Runx3, DAPK and CHFR is frequent in gastric cancer. DAPK and CHFR promoter hypermethylation may be an important help in evaluating the differentiation grade and lymph node status of gastric cancer. Weak gene expression and loss of gene expression due to promoter hypermethylation may be a cancer-specific event. Free full text available at www.tumorionline.it
Metastatic Pancreatic Cancer Response to Treatment with Cetuximab and Gemcitabine plus Capecitabine: A Case Report and Review of the Literature
Authors: Li Mei , Jiang Ming , Yan Xi , Wang Feng , Luo Feng
Published: February 2018

The treatment of pancreatic cancer remains a formidable challenge to clinicians. Here we describe the case of a 57-year-old man with metastatic pancreatic cancer who received combination treatment with cetuximab and capecitabine plus gemcitabine for four cycles. Repeat CT scan showed that the size of both the primary tumor in the pancreas and the metastatic lesions in the liver had shrunk significantly. Rapid reduction of the serum CA19-9 level was observed, and no serious toxic events occurred. The patient had a progression-free survival of eight months at the time we wrote this paper. The combination of cetuximab and capecitabine plus gemcitabine may be a useful therapy in metastatic pancreatic cancer. Free full text available at www.tumorionline.it
Isolated Splenic Metastasis of Ovarian Cancer 20 Years after Operation: A Case Report and Literature Review
Authors: Izuishi Kunihiko , Sano Takanori , Usuki Hisashi , Okano Keiichi , Masaki Tsutomu , Kushida Yoshio , Suzuki Yasuyuki
Published: February 2018

Splenic metastasis reflecting multiple metastases of cancer is often observed in the terminal stage, although solitary splenic metastasis is extremely rare. In addition, late recurrence even after 20 years of operation is very unusual. We report the case of a 52-year-old woman who was admitted to our department with a splenic tumor. She had a past history of total abdominal hysterectomy with bilateral sapingo-oophorectomy for ovarian cancer 20 years ago. Abdominal CT scan revealed a huge mass of 12 × 8 × 5.5 cm between the spleen and the left kidney. Splenectomy was performed with a diagnosis of splenic tumor. Microscopically, the tumor was a poorly differentiated adenocarcinoma including components of poorly differentiated ovarian cancer, and was diagnosed as an ovarian cancer metastasis. The patient showed no evidence of recurrence until 5 years postoperatively. Splenic metastasis is considered a terminal stage of cancer. However, when the lesion is solitary, surgical treatment is recommended. Free full text available at www.tumorionline.it
Quadruple Primary Malignancies of Liver, Bladder, Lung and Stomach in One Patient
Authors: Yhim Ho-Young , Kim Hee Sun , Lee Na-Ri , Kwak Jae-Yong , Yim Chang-Yeol , Park Ho Sung , Song Eun-Kee
Published: February 2018

Multiple primary malignancies are defined as two or more malignancies in an individual without any relationship between the tumors. Because of advances in the early detection, treatment, and supportive care for cancer, the number of cancer survivors has been gradually increasing, and this has led to an increase in the possible occurrence of subsequent malignancies. Recently, there have been reports that smoking is associated with a specific genetic mutation (the tumor suppressor gene TP53), and this genetic predisposition may be related to the development of multiple primary malignancies. Here we present a rare case of quadruple primary malignancies of the liver, bladder, lung and stomach, some of which possibly linked to smoking-related TP53 mutation. Because of its extreme rarity and the clear relationship between multiple primary malignancies and smoking-related TP53 mutation, we report this case along with a review of the relevant literature. Free full text available at www.tumorionline.it
2. Somatostatin and dopamine receptors
Authors: Ferone Diego
Published: February 2018

The discovery of the new properties of SSRs and DRs has led to a renewed interest in agents targeting these receptors and has opened new perspectives for medical treatment of patients with pituitary and neuroendocrine tumors resistant to the “classical”, currently available analogs. Moreover, SSRs and DRs crosstalk at membrane level may trigger alternative intracellular pathways or enhance the signalling for the control of cell growth. New somatostatin analogs and hybrid molecules, which display a broader and different spectrum of activities compared to conventional analogs, seem to be a promising therapeutic alternative for the control of hormone secretion and, hopefully, to reduce tumor burden. Receptor profile characterization is crucial for the accurate selection of patients potentially responsive to a given therapy. Free full text available at www.tumorionline.it
6. MEN syndromes
Authors: Falchetti Alberto
Published: February 2018

MEN1 and MEN2 are rare inherited cancer syndromes which express a variety of endocrine and nonendocrine tumors. The improved knowledge of molecular and clinical physiopathology of MEN syndromes, together with the availability of genetic testing, have led to earlier detection and intervention, with consequent reduction of mortality and morbidity for MEN-associated tumors. Genetic testing has gained a key role in the detection of asymptomatic patients harbouring mutations responsible for these syndrome, and allows institution of early and tailored intervention with a positive impact on the course of disease. Free full text available at www.tumorionline.it
7. False Positives and False Negatives in Neuroendocrine Tumors Diagnosis: Clinical Reports
Authors: Ducceschi Monika , Pusceddu Sara , Platania Marco
Published: February 2018

Differential diagnosis NETs may be highly challenging. In order to exclude conditions that may mimic a neuroendocrine neoplasms, a deep knowledge of all the aspects of the disease, together with an adequate capacity to interpret clinical data and imaging findings and to put them in right correlation, are strongly warranted. Patients which suspected neuroendocrine neoplasms should be referred to reference centers to receive optimal multidisciplinary care. Free full text available at www.tumorionline.it
Postoperative Radiotherapy in Prostate Cancer: Acquired Certainties and Still Open Issues. A Review of Recent Literature
Authors: Alongi Filippo , Cozzarini Cesare , Di Muzio Nadia , Scorsetti Marta
Published: February 2018

It is recognized that radiation therapy can eradicate microscopic tumor disease, even in postoperative prostate cancer patients, when extracapsular extension, positive surgical margins or increased prostate-specific antigen is found in surgical specimens. This review of recent literature analyzes and discusses acquired certainties and still open questions regarding type, timing, doses, techniques, toxicities, and associated hormonal therapies of radiotherapy prescribed after radical prostatectomy. Free full text available at www.tumorionline.it
Hepatic Arterial Infusion Chemotherapy for Liver Metastases from Gastric Cancer: An Analysis in Western Patients
Authors: Flörcken Anne , Schaefer Claudia , Bichev Dmitry , Breithaupt Kirstin , Dogan Yasemin , Schumacher Guido , Gebauer Bernhard , Riess Hanno , Dörken Bernd , Thuss-Patience Peter C
Published: February 2018

Aims and background

The advantage of administering chemotherapy by hepatic arterial infusion is the achievement of high drug concentrations in the liver. Oxaliplatin, irinotecan and 5-flourouracil are active agents in advanced gastric cancer. Therefore a retrospective analysis was performed to investigate the effects of these drugs administered by hepatic arterial infusion in heavily pretreated gastric cancer patients with predominant hepatic metastases. Very limited data about hepatic arterial infusion exist in western gastric cancer patients.

Methods

Seven patients with advanced gastric cancer were included in the retrospective analysis. All patients had proven progressive disease prior to initiation of hepatic arterial infusion. All had an ECOG performance status of ≤2 and had received at least two previous systemic chemotherapy regimens, including the combination of cisplatin/5-fluorouracil. Patients were given chemotherapy by hepatic arterial infusion: 5-fluorouracil, 600 mg/m2, together with folinic acid, 300 mg/m2/2 h, followed by oxaliplatin, 85 mg/m2/2 h, every 2 weeks.

Results

Fifty-four cycles of hepatic arterial infusion (range, 2–21) with a median treatment duration of 6 cycles were administered in 7 patients. The treatment was feasible and safe, no grade 3–4 toxicity was observed. One patient showed stabilization of liver metastases over 7 months. In 6 of the 7 patients there was radiologically proven progressive disease after a median treatment time of 10 weeks.

Conclusions

Chemotherapy by hepatic arterial infusion is modestly effective in heavily pretreated gastric cancer patients. Hepatic arterial infusion has a very favorable toxicity profile and can be safely administered even in elderly patients. It might be an additional therapeutic option and should be further investigated. The literature on hepatic arterial infusion in gastric cancer patients is reviewed. Free full text available at www.tumorionline.it
Systemic Chemotherapy with Pemetrexed and Cisplatin for Malignant Peritoneal Mesothelioma: A Single Institution Experience
Authors: Lainakis George , Zagouri Flora , Kastritis Efstathios , Sergentanis Theodoros N , Bozas George , Dimopoulos Meletios A , Papadimitriou Christos A
Published: February 2018

Background and aims

Primary malignant peritoneal mesothelioma is a rare malignancy with an unfavorable prognosis. Pemetrexed has proven effective in the treatment of malignant mesothelioma, alone or in combination with platinum agents. In the present study, chemo-naïve patients were evaluated for the efficacy and safety of the pemetrexed-cisplatin combination.

Methods

Six patients with diffuse peritoneal mesothelioma were treated with 6 cycles of pemetrexed (500 mg/m2) and cisplatin (75 mg/m2). Chemotherapy was administered on an outpatient basis every 3 weeks.

Results

Complete response was observed in 2 patients (33%) and partial response was observed in 3 patients (50%). The estimated median overall survival was 24 months and the estimated median time to disease progression was 9.5 months. The regimen was well tolerated.

Conclusions

Though our data reflect a small sample size, pemetrexed plus cisplatin accomplished a particularly high clinical benefit rate on chemo-naïve patients. Free full text available at www.tumorionline.it
Accuracy of Intraoperative Macroscopic Diagnosis of Sentinel Node Metastases in Breast Cancer: Is Accurate Prediction Possible?
Authors: Fujii Takaaki , Yanagita Yasuhiro , Kinoshita Teruhiko , Fujisawa Tomomi , Hirakata Tomoko , Yamaki Sayaka , Matsumoto Asuka , Uchida Nobuyuki , Iijima Misa , Kuwano Hiroyuki
Published: February 2018

Background

Accurate intraoperative diagnosis of sentinel lymph node (SLN) metastases enables the selection of patients who require axillary lymph node dissection, thus avoiding an additional operation. In this study we investigated the accuracy of intraoperative macroscopic diagnosis of SLN metastases in patients with breast cancer.

Methods

SLNs from 276 breast cancer patients with clinically negative nodes were analyzed by macroscopic examination. The results of intraoperative macroscopic diagnosis were compared with those of frozen section analysis.

Results

The sensitivity, specificity, overall accuracy, and false negative rate of SLN biopsy in the assessment of node status were 82.1%, 100%, 96.4%, and 17.9%, respectively, for frozen section analysis, and 57.1%, 95.5%, 87.7%, and 42.9%, respectively, for macroscopic evaluation. Even in patients with node metastasis >7 mm, the false negative rate of macroscopic evaluation was 11.1%.

Conclusions

Our results suggest that macroscopic diagnosis is less effective in predicting lymph node status in breast cancer than frozen section analysis. These findings imply that intraoperative macroscopic evaluation of sentinel nodes is never predictive of the final pathology. Free full text available at www.tumorionline.it
Expression Analysis of Angiogenesis-Related Genes in Bulgarian Patients with Early-Stage Non-Small Cell Lung Cancer
Authors: Metodieva Svetlana Nikolova , Nikolova Dragomira Nikolaeva , Cherneva Radostina Vlaeva , Dimova Ivanka Istalianova , Petrov Danail Borisov , Toncheva Draga Ivanova
Published: February 2018

Aims and background

Angiogenesis is a key process in the early stages of tumor development. In this study we aimed to evaluate the expression of a panel of angiogenesis-related genes in a group of Bulgarian patients with early-stage non-small cell lung cancer (NSCLC).

Methods and study design

We analyzed the expression of 84 genes associated with the angiogenic process in 12 NSCLCs of two histological subtypes: 7 adenocarcinomas and 5 squamous cell carcinomas. Eight peripheral nontumorous tissues were used as controls. We performed real-time PCR on pathway-specific gene arrays (SABiosciences).

Results

Our pilot study identified upregulated genes in early-stage NSCLC including growth factors (TGFA and EFNA3), the adhesion molecule THBS2, cytokines and chemokines (MDK, CXCL9, CXCL10), and the serine protease PLAU. Several genes showed downregulation including one growth factor (FIGF), the receptors for growth factors TEK and S1PR1 as well as adhesion molecules (COL4A3 and CDH5), the cytokine IL6, the matrix protein LEP and the transcription factor NOTCH4. The study demonstrated deregulated genes specific for the two histological subtypes including the transcription factor HAND2, which was overexpressed in squamous cell carcinomas but not adenocarcinomas.

Conclusions

Despite the limited number of patients, our results demonstrated the potential of angiogenesis-related genes as biomarkers in the early stages of NSCLC development. Free full text available at www.tumorionline.it
Immunohistochemical Assessment of MGMT Expression and p53 Mutation in Glioblastoma Multiforme
Authors: Lotfi Marziyeh , Afsharnezhad Sima , Raziee Hamid Reza , Ghaffarzadegan Kamran , Sharif Samaneh , Shamsara Jamal , Lary Sara , Behravan Javad
Published: February 2018

Aims and background

The prognosis of glioblastoma multiforme (GBM) remains poor despite advances in surgery and adjuvant therapies. TP53 and O6-methylguanine-DNA methyltransferase (MGMT) are tumor suppressor genes that are implicated in GBM resistance to radiation and chemotherapy. In order to assess the expression of the protein products of these two genes, 50 GBM samples were analyzed in this study.

Methods

Demographic and clinical data along with postsurgery tumor samples from 50 GBM patients were collected from the pathology archive. MGMT and p53 protein expression was evaluated by immunohistochemistry.

Results

52% of cases had mutated p53, predominantly expressed in the nuclei of tumor cells. MGMT immunohistochemistry was negative in 35 (70%) patients and positive in 15 (30%) others. Immunohistochemistry-negative specimens for MGMT expression showed a significantly higher expression of mutant p53 (P = 0.03).

Conclusion

MGMT expression was significantly lower in cells bearing p53 mutation. This indicates that there is a tendency for p53 activity to decline with MGMT inactivation. However, this study could not deduce which protein was the regulator of the other. Free full text available at www.tumorionline.it
Serum β-HCG and CA-125 as Tumor Markers in a Patient with Osteosarcoma: Case Report
Authors: Boss David S , Glen Hilary , Beijnen Jos H , de Jong Daphne , Wanders Jantien , Evans TR Jeffry , Schellens Jan HM
Published: February 2018

Background

Elevated β-HCG serum levels are usually an indication of pregnancy or pregnancy-related disorders, but β-HCG can also be elevated in testis and germ cell tumors. HCG expression by osteosarcoma is a rare phenomenon, with a few documented cases. CA-125 is commonly used to monitor disease progression and treatment response in ovarian cancer. CA-125 expression in patients with osteosarcoma has not previously been documented.

Case report

Elevated β-HCG and CA-125 serum levels were observed in a female patient of 57 years of age with metastatic osteosarcoma during screening investigations prior to participation in a phase I clinical trial. Pregnancy was excluded. Immunohistochemical studies revealed the tumor to be the source of the elevated β-HCG serum levels. We found no CA-125 expression in tumor tissue. The patient was treated with E7080, a novel oral multi-targeted tyrosine kinase inhibitor. We measured serum β-HCG and CA-125 to monitor treatment response. She had a significant clinical and radiological response after two cycles of treatment, but developed progressive disease after the third cycle. The β-HCG serum levels seemed to better reflect her disease status than those of the other tumor marker, CA-125.

Conclusions

When elevated, β-HCG serum levels in patients with osteosarcoma might be used to monitor treatment. Treatment of advanced osteosarcoma with tyrosine kinase inhibitors, including E7080, warrants further investigation. Free full text available at www.tumorionline.it
CIGNOweb.it
Authors: Truccolo Ivana , Bogliolo Anna , Ricci Roberto , Giacomini Mauro , Pivetti Susanna , Russell-Edu William , De Lorenzo Francesco , Della Seta Maurella , Colombo Cinzia , Bufalino Rosaria , Bocchini Giulia , Pierotti Marco , Lombardo Claudio , De Paoli Paolo
Published: February 2018

We introduce CIGNOweb.it, a database of oncology resources for patients, the general public and healthcare professionals. It builds on the previous Italian cancer resource Azaleaweb and offers quality-evaluated content. It meets international bibliographic and technical standards such as the Open Archives Initiative (OAI) for web content interoperability and the Functional Requirements for Bibliographic Records (FRBR) for bibliographic description with respect to the different media, applications, and user needs. Database content is supplied in collaboration with non-profit associations, libraries and the network of Cancer Information Points that is currently being established all over Italy. Expert and customer evaluation and feedback are provided for in the system. The graphic layout has been painstakingly designed to be user-friendly for a non-expert public. CIGNOweb.it is multicentric and will in time offer health information outside the field of oncology. It is designed to become a multilingual tool to organize, optimize and access patient information produced in the languages of the “newer” European countries. It is hoped that CIGNOweb.it will support other European nations in enhancing the structure and organization of their own-language patient health information and will contribute towards making a common health information portal of the European Union a reality. Free full text available at www.tumorionline.it