DIGESTIVE ENDOSCOPY, Issue 4 2006
Yasushi Adachi
Abnormal activation of growth factor receptors and their signal pathways are required for neoplastic transformation and tumor progression. The concept of targeting specific tumorigenic receptors has been validated by successful clinical application of multiple new drugs, such as those acting against HER2/neu, epidermal growth factor receptor 1, and c-Kit. In this review, we focus on the next promising therapeutic molecular target of insulin-like growth factor (IGF)-I receptor (IGF-Ir). The IGF/IGF-Ir system is an important modifier of cancer cell proliferation, survival, growth, and treatment sensitivity in a number of neoplastic diseases, including human gastrointestinal carcinomas. Preclinical studies demonstrated that downregulation of IGF-Ir signals reversed the neoplastic phenotype and sensitized cells to antitumor treatments. We summarize a variety of ways to disrupt IGF-Ir function. Then, we introduce our strategy of adenoviruses expressing dominant negative of IGF-Ir (IGF-Ir/dn) against gastrointestinal cancers, including stomach, colon, and pancreas. IGF-Ir/dn suppresses tumorigenicity both in vitro and in vivo and increases stressor-induced apoptosis. IGF-Ir/dn expression upregulates chemotherapy-induced apoptosis and these combination therapies with chemotherapy are very effective against tumors in mice. Some drugs blocking IGF-Ir function are now entering clinical trial, thus IGF-Ir might be a candidate for a therapeutic target in several gastrointestinal malignancies. [source]

SUCCESSFUL PLACEMENT OF SELF-EXPANDABLE METALLIC STENTS FOR DOUBLE COLORECTAL CANCERS

DIGESTIVE ENDOSCOPY, Issue 4 2006
Tsuyoshi Abe
Stent placement for the palliation of unresectable colon cancer is an alternative to surgical treatment that has recently become popular. A dedicated stent for colorectal cancer is not available in Japan. We report a patient with two colonic obstructions who underwent a successful palliative treatment using two stents. He was admitted to Toho University Ohashi Medical Center because of ileus. A colonoscopy revealed two advanced lesions with stenosis in the sigmoid and transverse colon. Because he had multiple liver metastases and severe Alzheimer dementia, we selected palliative stent placement for the treatment of both strictures. We placed a covered stent in the sigmoid colon stricture and subsequently attempted to place a second stent in the transverse colon stricture. However, the second stent could not be placed in the transverse colon because the modified delivery system could not pass through the first stent in the sigmoid colon. This probably led to a twisting of the stent in the sigmoid colon. We next used the 24 F introducer sheath that is included in Keller-Timmermans Introducer Sets. This strategy allowed the modified delivery system to be easily passed through the initial stent in the sigmoid colon and then advanced into the transverse colon stricture, enabling both stents to be positioned properly. [source]

Trials update in wales

CYTOPATHOLOGY, Issue 2007
A. Fiander
Three ongoing studies will be presented and discussed. Prevalence of Human Papillomavirus Infection in a South Wales Screening population Methods: A total of 10 000 consecutive, anonymous liquid based cytology screening samples were collected over a five month period in 2004. Age, cytology result and social deprivation score was provided for each specimen. The methodology was chosen to ensure inclusion of all women attending routine cervical screening, avoiding potential constraints associated with obtaining individual informed consent. The liquid based cytology samples were processed and reported by the receiving cytology laboratory and the residual specimens sent to the HPV Research Laboratory, Wales College of Medicine, where they were processed and stored at -80°C until analysis. High risk and low risk HPV Typing was undertaken using PCR , EIA (Jacobs et al 1997). Full high risk typing was performed on HPV positive specimens. Results: The study population had a mean age of 38 years with 92% negative, 5% borderline and 3% dyskaryotic cytology. The average social deprivation score was 17.4 (based upon the Welsh Index of multiple deprivation). The following results will be presented: HPV prevalence by age. HPV prevalence by cytology result. Type specific HPV prevalence in single and multiple infection. Conclusion: This study represents the largest type specific HPV Prevalence Study in the UK to date. As such it will form a useful base line against which to access performance of marketed HPV tests and evaluating the impact following implementation of HPV vaccination. [Funded by Welsh Office for Research and Development] CRISP , 1 Study (Cervical Randomized Intervention Study Protocol -1) Background: Indole-3-carbinol (I3C) and Diindolylmethane (DIM) are found in cruciferous vegetables and have been identified as compounds that could potentially prevent or halt carcinogenesis. I3C spontaneously forms DIM in vivo during acid digestion. I3C has been shown to prevent the development of cervical cancer in HPV 16 transgenic mice and both I3C and DIM have been shown to promote cell death in cervical cancer cell models. DIM is the major active bi-product of I3C and preliminary data indicate that DIM is active in cervical dysplasia and may be better tolerated than I3C. Aim: To investigate chemoprevention of high grade cervical neoplasia using Diindolylmethane (DIM) supplementation in women with low grade cytological abnormalities on cervical cytology. Objectives: To observe any reduction in the prevalence of histological proven high-grade cervical intraepithelial neoplasia (CIN) after 6 months of supplementation. ,,To observe any reduction in the prevalence of cytological abnormalities. ,,To observe any changes in the clinical appearance of the cervix. To assess acceptability and monitor any side effects of DIM supplementation. ,,To assess whether any benefit is seen in relation to Human Papillomavirus (HPV) status including HPV Type, Viral load and integration. Methods: This is a double blind randomized placebo-controlled trial involving 600,700 women with low grade cytological abnormalities on a cervical smear. Randomization is in the ratio of 2 : 1 in favour of active medication. Women with first mildly dyskaryotic smear or second borderline smear are eligible. They are asked to take two capsules daily for 6 months. At the end of 6 months they undergo repeat cervical cytology, HPV testing and colposcopy. Results: A progress report will be given for this ongoing study. [Funded: - Cancer Research UK] Type Specific HPV Infection in Welsh Cervical Cancers Background: Whilst there have been numerous studies of HPV infection associated with cervical cancer and on prevalence of Human Papillomavirus in diverse populations there have been no studies of these variables in the same population. Against a background of prophylactic HPV vaccination it is important to assess potential protection against cervical cancer within a given population. The most comprehensive analysis of HPV type specific cervical cancer is a meta-analysis published by the IARC in 2003. This however included only three UK based studies, totalling 118 cases, 75 of which were only investigated by HPV type PCR for four high risk types. None of this data was presented with associated population based prevalence data. Therefore, the research objectives for this study in combination with the first study above, are as follows: To determine the frequency of specific HPV types in cervical cancers in Wales. To compare the distribution of specific HPV types amongst cervical cancers with their prevalence in the general population. This will allow accurate delineation of the relationship between prevalence of specific HPV types in the general population and their association with clinically relevant disease. This information is a pre-requisite to assess the potential impact of prophylactic vaccination against HPV infection in Wales. Methods: Welsh Cervical Cancer specimens from 2000,2005 will be identified from pathology departments within Wales. The pathology of each tumour will be reviewed by a single Gynaecological Pathologist. The age of the patient and pathological features of the tumour will be noted. DNA will be extracted from the paraffin sections and HPV typed by PCR-EIA. Results: A progress report will be given for this ongoing study. [Funded by Welsh Office for Research and Development] [source]

Sentinel Lymph Node Biopsy for High-Risk Nonmelanoma Skin Cancers

DERMATOLOGIC SURGERY, Issue 7 2007
RACHEL E. SAHN
BACKGROUND Although the utility of the sentinel lymph node biopsy (SLNB) in the staging of melanoma is well established, its usefulness in high-risk nonmelanoma skin cancer (NMSC) is yet to be determined. OBJECTIVE The objective was to report our experience with patients who underwent SLNB for the staging of a high-risk NMSC. MATERIALS AND METHODS We identified 13 patients with a high-risk NMSC who underwent SLNB between 1998 and 2006 and conducted a retrospective review of their medical records and tumor pathology. Their status as regards tumor recurrence and survival was obtained when possible. RESULTS Of 13 patients, 9 had squamous cell carcinoma (SCC), 2 had sebaceous gland carcinoma, 1 had porocarcinoma, and 1 had atypical fibroxanthoma. All SLNB were negative for metastatic disease, but 1 appeared to be a false-negative finding. CONCLUSION Compared to melanoma, SCC of the skin are much less predictable as regards their tendency to metastasize to the regional lymph nodes. Although the SLNB appears to be a reliable staging procedure for NMSC (especially SCC), the yield may be too low to justify its routine use in this patient population. More data are needed to determine when a SLNB is justified in the management of NMSC. [source]

Curettage prior to Mohs' Micrographic Surgery for Previously Biopsied Nonmelanoma Skin Cancers: What Are We Curetting?

DERMATOLOGIC SURGERY, Issue 1 2005
Comparative Study, Prospective, Retrospective
Background Curettage prior to excision and Mohs' micrographic surgery for nonmelanoma skin cancer is performed based on the assumption that the curette will remove softer, more friable tumor-infiltrated dermis and leave structurally intact normal skin. This assumption, however, has not been objectively examined in the dermatologic surgery literature. Objective We performed a study to examine the ability of curettage to selectively remove and delineate nonmelanoma skin cancer prior to Mohs' micrographic surgery. Methods The study included 150 previously biopsied basal cell and squamous cell carcinomas less than 1.5 cm in size. We conducted (1) a retrospective study of 50 tumors curetted prior to Mohs' surgery by a surgeon who routinely curettes preoperatively; (2) a prospective study in which a surgeon who routinely does not curette preoperatively curetted 50 tumors prior to Mohs' surgery; and (3) a comparative historical group of 50 noncuretted tumors treated with Mohs' surgery by the latter surgeon. All curetted tissue was evaluated histologically. Results Only 50% of the curetted tissue demonstrated the presence of tumor in the curettings, but in 76% of these, the curette left residual tumor at the surgical margins. Of the other 50% in which the curette removed only non,cancer-containing skin, 34% had tumor present at the surgical margin. Overall, the curette removed tumor, leaving no residual tumor at the surgical margins in only 12% of lesions. Comparison with historical noncuretted tumors operated on by the same surgeon showed that curettage did not affect the mean number of stages or the proportion of tumors requiring more than one stage for histologic clearance. Conclusion Although curettage may be helpful in debulking friable skin prior to Mohs' micrographic surgery, it does not reliably delineate the extent of a tumor. MING H. JIH, MD, PHD, PAUL M. FRIEDMAN, MD, LEONARD H. GOLDBERG, MD, AND ARASH KIMYAI-ASADI, MD, HAVE INDICATED NO SIGNIFICANT INTEREST WITH COMMERCIAL SUPPORTERS. [source]

Rhinophyma and Coexisting Occult Skin Cancers

DERMATOLOGIC SURGERY, Issue 2 2001
Michael E. Lutz MD
Background. Although coexistent tumors have been reported in patients with rhinophyma, few reports have described the coexistence of rhinophyma and an occult infiltrating squamous cell carcinoma (SCC). Objective. Preoperatively and during rhinophymaplasty, recognition of subtle changes can suggest an underlying malignancy. Methods. A large infiltrating SCC was noted during electrosurgical rhinophymaplasty. Mohs micrographic surgery was performed to clear the tumor. Results. The patient was tumor-free with no evidence of recurrence at 1-year follow-up. Conclusion. In the evaluation of changing rhinophyma or subtle changes in tissue noted during rhinophymaplasty, physicians must consider the possibility of an underlying malignancy. [source]

Discussant's Comment 1: The Best Endoscopic Measure for Early Gastric Cancers is Endoscopic Mucosal Resection with a Cap Method

DIGESTIVE ENDOSCOPY, Issue 2000
Atsushi Kawaguchi
No abstract is available for this article. [source]

Helicobacter pylori Infection may be Implicated in the Topography and Geographic Variation of Upper Gastrointestinal Cancers in the Taihang Mountain High-Risk Region in Northern China

HELICOBACTER, Issue 5 2010
Denggui Wen
Abstract Backgrounds:,Helicobacter pylori infection is prevalent in China. Chronic infection of the bacterial not only causes distal stomach cancer, but also confers risk to gastric cardia adenocarcinoma. Because H. pylori infection is inversely associated with esophageal adenocarcinoma, globally the infection rate is significantly correlated with the ratio of squamous carcinoma to adenocarcinoma of the esophagus. These agree with the topography of upper gastrointestinal cancer observed in the Taihang Mountain high-risk region where both gastric cardia and non-cardia adenocarcinoma coincide with esophageal squamous cancer, but with almost no distal esophageal adenocarcinoma. Moreover, as altitude increases from plain to mountains, we observed progressively increasing incidence rates of gastric adenocarcinomas in recent years in the region. Because H. pylori infection is a definite carcinogen to gastric adenocarcinoma and is more prevalent in the mountain than in plain areas due to undeveloped living conditions, the observation gives the impression as though H. pylori infection is implicated. Aims:, This article aims to note the role of H. pylori infection in upper gastrointestinal cancer in the Taihang Mountain high-risk region in northern China. Materials and Methods:, First the unique topography and geographic variation of upper gastrointestinal cancer in the region is described to indicate a possible role of H. pylori infection, then we review studies on prevalence of H. pylori infection in the high-risk region and describe difference in socioeconomic development and water hygiene between the plains and the mountains as related to the prevalence of H. pylori infection. Results:, Coincidence of gastric cancer in the region and a progressively increasing rate of the cancer from the plain towards the mountains indicate H. pylori infection may be implicated in upper gastrointestinal cancer. Conclusion:, International collaboration is needed to study H. pylori and upper gastrointestinal cancer in the region when rapid industrialization is just beginning. [source]

Biological aggressiveness of prostate cancer in the Finnish screening trial

INTERNATIONAL JOURNAL OF CANCER, Issue 3 2009
Marita Laurila
Abstract Prostate cancer aggressiveness was evaluated based on pathologic characterization of cases detected in the Finnish prostate cancer screening trial. The trial population consists of 80,458 men aged 55,67 years. A total of 32,000 men were randomized to the screening arm. The remaining 48,000 men formed the control arm. The interval cases and cancers among nonparticipants and in the control arm were identified from the Finnish Cancer Registry. Random samples were selected from screen-detected cases (126 of 543 in the first and 133 of 508 in the second round) and control arm cancers (133 out of 863), in addition to all 92 interval cancers and 106 cases among nonparticipants. All the biopsies were regraded according to the Gleason system. The expression of the proliferation antigen Ki-67 was determined in 479 cases (72%). More than half of the tumors diagnosed in the first round of screening were high-grade cancers (Gleason 7 or higher). In the second round, the proportion of low-grade cancers increased from 47% to 70%. Cancers in the screening arm were more commonly focal and fewer bilateral cancers were detected. The cancers among nonparticipants were the most aggressive group. The aggressiveness of the interval cancers was between the cancers detected in the first and the second round. Our results indicate that prostate cancers detected through screening are less biologically aggressive. This was most notable after the first screening round. Nonparticipants had more aggressive cancers. © 2008 Wiley-Liss, Inc. [source]

Parental lung cancer as predictor of cancer risks in offspring: Clues about multiple routes of harmful influence?

INTERNATIONAL JOURNAL OF CANCER, Issue 3 2006
Kari Hemminki
Abstract The carcinogenic effects of active smoking have been demonstrated for many sites, but the effects of passive smoking and exposures during pregnancy and breastfeeding are less well documented. We examined whether 0,70-year-old offspring of parents with lung cancer are at a risk of cancer that cannot be explained by their smoking or familial risk. It was assumed that known target sites for tobacco carcinogenesis would be affected, if any. The nationwide Swedish Family-Cancer Database with cancers recorded from 1958 to 2002 was used to calculate age-specific standardized incidence ratios (SIRs). Among offspring of affected mothers, increased risks were observed for upper aerodigestive (SIR 1.45), nasal (2.93), lung (1.71) and bladder (1.52) cancers and for kidney cancer (6.41) in one age group. The risk of bladder cancer was found in younger age groups than that of lung cancer. Cancers at many of these sites, but not the kidney or the bladder, were in excess in offspring of affected fathers. Nasal cancer was even increased when either parent was diagnosed with lung cancer; the highest risk was for nasal adenoid cystic carcinoma (7.73). The data suggest that passive smoking during childhood is associated with an increase risk of nasal cancer. For bladder and kidney cancers, a contribution by tobacco carcinogens is implicated through breastfeeding and in utero exposure. © 2005 Wiley-Liss, Inc. [source]

Genetic Aberrations in Chernobyl-Related Thyroid Cancers: Implications for Possible Future Nuclear Accidents or Nuclear Attacks

IUBMB LIFE, Issue 12 2003
Gennady Ermak
Abstract Cases of thyroid cancer among children in Belarus represent a unique model system in which the cause of the cancer is known - radiation. Although other sources of radiation-induced cancers are diminishing (survivors of Hiroshima and Nagasaki, and individuals exposed to diagnostic or therapeutic radiation) fears of radiation exposure from accidents and terrorism are increasing. Our analysis of current data reveals that Chernobyl-related cancer cases might have a specific pattern of genetic aberrations. These data strongly confirm the hypothesis that radiation-induced cancers might arise as a result of specific gene aberrations that are distinct from those in sporadic cancers, suggesting that methods of prevention and treatment of radiation-induced cancers might require a different approach. Understanding of the molecular mechanisms of Chernobyl-related papillary thyroid carcinomas will help to identify mechanisms by which radiation causes aberrations and oncogenic cell transformation. Thus, in turn, it will be important in the development of new treatments or technologies to minimize the effects of radiation damage from nuclear accidents or nuclear attacks. IUBMB Life, 55: 637-641, 2003 [source]

Review of Research Studies That Evaluated the Impact of Treatment for Childhood Cancers on Neurocognition and Behavioral and Social Competence: Nursing Implications

JOURNAL FOR SPECIALISTS IN PEDIATRIC NURSING, Issue 2 2000
Julia Challinor
ISSUES AND PURPOSE. Given the increasing incidence of childhood cancer, increasing survivor rates, and documented incidence of sequelae, nurses need evidence on which to base interventions for families at risk. The authors review and critique research studies that evaluated the impact of treatment for childhood cancers. Implications for nursing practice are discussed. CONCLUSIONS. Research to evaluate the effects of treatment on neurocognition and behavioral and social competency of children with cancer has produced conflicting results. Most studies found deleterious effects on all three areas associated with childhood cancer treatment. Some studies, however, found no differences between childhood cancer survivors and children on therapy compared to normative data or healthy controls. PRACTICE IMPLICATIONS. Knowledge of the short-and long-term impact of treatment for childhood cancer on neurocognition and behavioral and social competence allows nurses to design interventions that mitigate neurocognitive effects, decrease behavioral problems, and improve social competence. [source]

Biomarkers, regerons, and pathways to lethal cancer,

JOURNAL OF CELLULAR BIOCHEMISTRY, Issue 5 2007
Meng Qiao
Abstract Cancer is a disease of "outlaw" cells that become mutated in regulatory mechanisms. They have lost normal self controls and relationships to the whole organism. Cancers can progress by several pathways from a normal cell to malignant cancer, from bad to worse. Questions about advisability of treatment for some cancers arise from the possibility that they are arrested during progression and so never become lethal. Techniques could be developed to determine the degree of progression and possibility for successful treatment. This article is intended to suggest a way of looking at cancer. It is not a review so references to research articles are infrequent. J. Cell. Biochem. 102: 1076,1086, 2007. © 2007 Wiley-Liss, Inc. [source]

Invasive breast cancers detected by screening mammography: A detailed comparison of computer-aided detection-assisted single reading and double reading

JOURNAL OF MEDICAL IMAGING AND RADIATION ONCOLOGY, Issue 5 2009
JN Cawson
Summary To compare double reading plus arbitration for discordance, (currently best practice, (BP)) with computer-aided-detection (CAD)-assisted single reading (CAD-R) for detection of invasive cancers detected within BreastScreen Australia. Secondarily, to examine characteristics of cancers detected/rejected using each method. Mammograms of 157 randomly selected double-read invasive cancers were mixed 1:9 with normal cancers (total 1569), all detected in a BreastScreen service. Cancers were detected by two readers or one reader (C2 and C1 cancers, ratio 70:30%) in the program. The 1569 film-screen mammograms were read by two radiologists (reader A (RA) and reader B(RB)), with findings recorded before and after CAD. Discordant findings with BP were resolved by arbitration. We compared CAD-assisted reading (CAD-RA, CAD-RB) with BP, and CAD and arbitration contribution to findings. We correlated cancer size, sensitivity and mammographic density with detection methods. BP sensitivity 90.4% compared with CAD-RA sensitivity 86.6% (P = 0.12) and CAD-RB 94.3% (P = 0.14). CAD-RB specificity was less than BP (P = 0.01). CAD sensitivity was 93%, but readers rejected most positive CAD prompts. After CAD, reader's sensitivity increased 1.9% and specificity dropped 0.2% and 0.8%. Arbitration decreased specificity 4.7%. Receiving operator curves analysis demonstrated BP accuracy better than CAD-RA, borderline significance (P = 0.07), but not CAD-RB. Secondarily, cancer size was similar for BP and CAD-R. Cancers recalled after arbitration (P = 0.01) and CAD-R (P = 0.10) were smaller. No difference in cancer size or sensitivity between reading methods was found with increasing breast density. CAD-R and BP sensitivity and cancer detection size were not significantly different. CAD-R specificity was significantly lower for one reader. [source]

Cancer as a consequence of the rising level of oxygen in the Late Precambrian

LETHAIA, Issue 3 2007
JOHN M. SAUL
The origin of multicelled animal life required collagen-family molecules whose own formation depended on the availability of molecular oxygen. Cancers, by contrast, are characterized by their low use of oxygen. In discussing the relationship between the origin of multicelled life and the origin of cancer, it is useful to think in terms of tissues rather than individual cells or complete animals. When animal tissues are disturbed, their constituent cells may be partially released from the constraints of multicellularity. This permits or obliges cells to reactivate anaerobic metabolic ways used by their single-celled ancestors in the oxygen-deficient Precambrian seas. Inhibition or loss of cell respiration under such circumstances may cause reversion to glycolytic fermentation, a less efficient metabolic style that generates waste products that are retained, thereby producing excess cell-growth. Distortion of tissue architecture may ensue with impairment of cell-to-cell adhesion, thereby liberating individual cells. Cells freed from tissue constraints undergo Darwinian variation which leads to loss of differentiation and produces cell types that are incompatible with the normal functioning of tissues. These steps, which may manifest themselves as carcinogenesis, are not reversible by restoration of oxygen and in effect constitute a demergence from the metazoan state. The existence of cancer among diverse phyla and especially among domesticated animals, suggests that the risk of cancer may be an initial condition of complex multicellular life and that it remains preferentially associated with newly modified designs. If so, there would be therapeutic strategies that have not yet been adequately considered. ,Cambrian explosion, cancer, cell differentiation, collagen, glycolysis, hard parts, metazoan origins. [source]

Review article: a conceptual approach to understanding the molecular mechanisms of cancer development in Barrett's oesophagus

ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 8 2001
R. F. Souza
Oesophageal adenocarcinoma is one of the most deadly human malignancies. Gastro-oesophageal reflux disease (GERD) has been established as a strong risk factor for oesophageal adenocarcinoma, and more than 40% of adult Americans experience regular GERD symptoms. GERD can be complicated by oesophagitis, and by replacement of oesophageal squamous mucosa with metaplastic, intestinal-type epithelium (Barrett's oesophagus) that is predisposed to malignancy. Cancers in Barrett's oesophagus arise through a sequence of genetic alterations which endow unlimited proliferative capacity upon the cells by affecting components of the cell cycle clock apparatus,the pivotal molecular machinery in the cell nucleus that controls whether a cell will proliferate, differentiate, become quiescent or die. This report describes how the genetic abnormalities that have been recognized in Barrett's oesophagus might promote carcinogenesis through effects on the cell cycle clock machinery. The goal of this review is to provide the clinician with a useful conceptual basis for evaluating studies on the molecular mechanisms underlying the progression from metaplasia to carcinoma in Barrett's oesophagus. [source]

Estrogen and its receptors in cancer

MEDICINAL RESEARCH REVIEWS, Issue 6 2008
George G Chen
Abstract The involvement of estrogen and its receptors in the development of cancer has been known for years. However, the exact mechanism responsible is far from clear. The estrogen-mediated carcinogenic process is complicated by recent findings, which reveal that estrogens have multiple functions in cells, which can be either adverse or beneficial, and that the effects of estrogen may be cell-type or organ dependent. The estrogenic effect may be also greatly influenced by the state of two estrogen receptors, ER, and ER,. This review will discuss the role and function of estrogens and its receptors in cancers of three categories: (1) Breast cancer and gynecologic cancers, (2) Cancers of endocrine organs, (3) Lung cancer and cancers of digestive system. We will also review some novel treatments aiming to interfere with relevant pathways mediated by estrogens and its receptors. © 2008 Wiley Periodicals, Inc. Med Res Rev, 28, No. 6, 954,974, 2008 [source]

Clinical Pain Research: Challenges Across Cancers, Cultures, and Disciplines

PAIN MEDICINE, Issue 1 2001
Article first published online: 21 DEC 200
No abstract is available for this article. [source]

Photodynamic Therapy Treatment of Early Oral and Laryngeal Cancers,

PHOTOCHEMISTRY & PHOTOBIOLOGY, Issue 5 2007
Merrill A. Biel
Photodynamic therapy (PDT) is a nonsurgical, minimally invasive treatment that uses a light source to activate light-sensitive drugs or photosensitizers in the treatment of cancer and other diseases. PDT has been successfully employed to treat early carcinomas of the oral cavity and larynx preserving normal tissue and vital functions of speech and swallowing. Two hundred seventy-six patients with early carcinomas of the oral cavity and larynx were treated from 1990 to 2006. Cure rates with a single treatment for early laryngeal and oral cancers were 91% and 94%, respectively. PDT is an effective primary and alternative treatment modality for early oral cavity and laryngeal cancers. [source]

Cyclooxygenase-2 Expression in Murine and Human Nonmelanoma Skin Cancers: Implications for Therapeutic Approaches,

PHOTOCHEMISTRY & PHOTOBIOLOGY, Issue 1 2002
Kathy P. An
ABSTRACT Inflammatory stimuli result in the production of cutaneous eicosanoids, which are known to contribute to the process of tumor promotion. Cyclooxygenase (COX), the rate-limiting enzyme for the production of prostaglandins (PG) from arachidonic acid, exists in at least two isoforms, COX-1 and COX-2. COX-1 is constitutively expressed in most tissues and plays various physiological roles, whereas increased COX-2 expression is known to occur in several types of epithelial neoplasms. Enhanced PG synthesis is a potential contributing factor in UVB-induced nonmelanoma skin cancers (NMSC). Increased COX-2 staining occurs in murine skin neoplasms after chronic exposure to carcinogenic doses of UVB. In this study, immunohistochemical and Western blot analyses were employed to assess longitudinally COX-2 expression in a standard mouse UVB complete carcinogenesis protocol and in human basal cell carcinomas (BCC) and squamous cell carcinomas (SCC). During UVB irradiation of mice, COX-2 expression consistently increased in the hyperplastic skin, the benign papillomas and the SCC. COX-2 expression was also increased in human actinic keratoses, SCC and BCC as well as in murine SCC and BCC. The pattern of COX-2 expression was quite variable, occurring in a patchy distribution in some lesions with staining confined mainly to suprabasal cell layers. In general, COX-2 expression progressively became more extensive in benign papillomas and well-differentiated murine SCC. The staining was predominantly cytoplasmic and perinuclear in some focal areas in tissue stroma around both murine and human tumors. Western blot analysis confirmed negative COX-2 expression in normal skin, whereas acute UVB exposure resulted in increased enzyme expression, which continued to increase in developing papillomas and SCC. Because of the evidence indicating a pathogenic role for eicosanoids in murine and human skin neoplasms, we performed studies to assess the anti-inflammatory and anticarcinogenic effects of green tea extracts, which are potent antioxidants. Acute exposure of the human skin to UVB (minimum erythema dose × 4) caused a transient enhancement of the COX-2 expression, which reverted to baseline within hours; however, in murine skin the expression persisted for several days. Pretreatment with the topically applied green tea extract (1 mg/cm2) largely abrogated the acute COX-2 response to UVB in mice or humans. In summary, enhanced COX-2 expression serves as a marker of epidermal UVB exposure for murine and human NMSC. These results suggest that COX-2 inhibitors could have potent anticarcinogenic effects in UVB-induced skin cancer. [source]

Latest news and product developments

PRESCRIBER, Issue 6 2008
Article first published online: 24 APR 200
Government responds to NICE report The Government has published its response to the Health Select Committee's report into NICE, broadly arguing that the Committee's recommendations are either already being dealt with or are not appropriate. The Committee recommended appraisals for all new drugs, shorter, rapid appraisals to coincide with their launch, and improved mechanisms for setting drug prices. The Government says its negotiations on the PPRS preclude a detailed response but suggests a rapid system may not be transparent or legally robust. It is exploring how high-cost drugs can be brought within the payment-by-results tariff. While defending NICE's reliance on QALYs, the Government accepts the need to explore how wider economic factors can be considered. As for the threshold cost per QALY by which NICE defines cost effectiveness, it says this is being validated scientifically and NICE will continue to determine the threshold. More topically, the Committee criticised the quality of clinical trial data available to NICE. The Government sees no need to compel pharmaceutical companies to disclose information and says NICE is already becoming more involved with research programmes. All clinical trials must be registered (confidentially) with the EU and the Government believes mandatory registration in the UK would be ineffective and illegal. Prescription charge up again from April The Government has raised the prescription charge by 25p to £7.10 per item with effect from 1 April. Prescription prepayment certificates will cost £27.85 for three months and £102.50 for 12 months. The increase, below the annual rate of inflation for the 10th successive year, will be levied on the 12 per cent of prescriptions that are liable for the charge: 5 per cent via prepayment certificates and 7 per cent from other prescriptions. The charge will generate £435 million in England in 2008/09; this excludes money from prescriptions written by dispensing doctors, which is retained by the PCT. Following criticism of the charge by the Health Select Committee, the Government says it has reviewed the charge and is now consulting on ,cost-neutral' options. MHRA safety update The MHRA warns of possible dose errors associated with Boots Medisure Domiciliary Dosage System in its latest issue of Drug Safety Update (2008;1:issue 8). One case has been reported in which incomplete sealing allowed tablets to mix between compartments. No other cases are known and the MHRA says no harm was reported but the risk is serious. The system should be carefully sealed and inspected visually and physically. The MHRA reaffirms its plans to reclassify all pseudoephedrine and ephedrine products to prescription-only status in 2009 if the new restrictions on sales do not reduce misuse. Other topics in this month's Update include revised indications for oral ketoconazole (Nizoral), restricting its use to selected conditions unresponsive to topical therapy; reformulation of the injectable antibiotic Tazocin (piperacillin plus tazobactum); the risk of peripheral neuropathy associated with pegylated interferon and telbivudine (Sebivo) in the treatment of hepatitis B; and serious adverse events associated with modafinil (Provigil). First oral anticoagulant since warfarin In January this year the EMEA issued a positive opinion to recommend marketing authorisation of the oral, fixed-dose, direct thrombin inhibitor dabigatran etexilate (Pradaxa) for the primary prevention of venous thromboembolism (VTE) in adult patients that have undergone elective knee or hip replacement surgery. Marketing authorisation for the EU (including the UK) is expected from the European Commission in the next few weeks, making dabigatran the first oral anticoagulant since warfarin was introduced in 1954. Dabigatran etexilate has been shown to be as safe and effective as enoxaparin (Clexane) with a similar adverse event profile in the noninferiority phase III RENOVATE (Lancet 2007;370: 949-56) and RE-MODEL (J Throm Haemost 2007;5:217885) trials, which investigated the efficacy and safety of dabigatran compared to enoxaparin in reducing the risk of VTE after total hip and knee surgery respectively. Dabigatran has the practical advantage over low-molecular-weight heparin of oral postoperative administration and no risk of heparin-induced thrombocytopenia and, unlike warfarin, does not require monitoring or dose titration. Risk scale predicts anticholinergic effects US investigators have developed a scale for predicting the risk of anticholinergic side-effects from older patients' medicines (Arch Intern Med 2008;168: 508-13). The scale assigns a score from 1 (low) to 3 (high) for the risk of anticholinergic effects such as dry mouth, constipation and dizziness associated with commonly prescribed medicines. Checking the scale retrospectively in older patients in residential care, a higher score was associated with a 30 per cent increased risk of side-effects after adjustment for age and number of medicines. When this was repeated prospectively in a primary-care cohort, the increased risk was 90 per cent. HRT cancer risk persists The latest analysis of the Women's Health Initiative (WHI) trial of HRT shows that the small increase in the risk of cancer persists for up to three years after stopping treatment (J Am Med Assoc 2008;299:1036-45). WHI was stopped after 5.6 years' follow-up when it became clear the risks of HRT outweighed its benefits. This follow-up after a further three years (mean 2.4) involved 15 730 women. The annual risk of cardiovascular events was similar for HRT (1.97 per cent) and placebo (1.91 per cent). Cancers were more common among women who had taken HRT (1.56 vs 1.26 per cent), in particular breast cancer (0.42 vs 0.33 per cent). All-cause mortality was higher, but not statistically significantly so, with HRT (1.20 vs 1.06 per cent). Tight glycaemic control may increase falls Maintaining HbA1C at or below 6 per cent with insulin is associated with an increased risk of falls, a US study suggests (Diabetes Care 2008;31:391-6). The Health, Aging and Composition study involved 446 older people with type 2 diabetes (mean age 74) followed up for approximately five years. The incidence of falls ranged from 22 to 30 per cent annually. Comparing subgroups with HbA1C of ,6 per cent and >8 per cent, an increased risk of falls was associated with insulin use (odds ratio 4.4) but not oral hypoglycaemic drugs. Copyright © 2008 Wiley Interface Ltd [source]

Pulmonary complications of immune reconstitution inflammatory syndromes in HIV-infected patients

RESPIROLOGY, Issue 4 2009
Kristina CROTHERS
ABSTRACT Immune reconstitution inflammatory syndrome (IRIS) describes a paradoxical worsening of clinical status related to recovery of the immune system, as can occur after the initiation of highly active antiretroviral therapy (HAART) in HIV-infected patients. Most commonly, IRIS results from opportunistic infections that can unmask or develop paradoxical worsening following HAART. Cancers, autoimmune conditions and sarcoidosis have also been associated with IRIS. Pulmonary complications may be frequently encountered. This article reviews the types and clinical presentation of IRIS, with a focus on the pulmonary manifestations. Management and outcome of IRIS are considered. [source]

Chemopreventive Effect of Celecoxib in Oral Precancers and Cancers,

THE LARYNGOSCOPE, Issue 10 2006
Lining Feng PhD
Abstract Objectives: Oral cancer has become an important health care problem in many countries. Because this disease develops slowly, early detection and intervention can greatly affect ultimate outcome. Celecoxib is a cyclooxygenase-2 inhibitor with significantly less toxicity. This study investigated the possibility of using it for chemoprevention of oral cancer at the early stages. Study Design: Randomized animal study. Methods: Dysplastic lesions were induced in the buccal pouches of 47 hamsters by a 5 week painting of 9,10-dimethl-1,2-benzanthrancene (DMBA). Basal diets or diets containing 500 or 1,500 ppm of Celecoxib were orally given for 7 weeks. The T50 (50% incidence; i.e., the time to appearance of tumors in 50% of the hamsters) was observed, and volume of tumors was measured on day 1, 9, 19, 28, 35, and 48 with the Celecoxib treatment. Results: The T50 was 9, 19, and 28 days with the treatment in the control group, in the 500 ppm group, and in the 1,500 ppm group, respectively. It indicated that the Celecoxib treatment could delay progression of early lesion. The tumor measurement showed that this treatment was also effective in delaying tumor growth in both treatment groups. There was a difference in the treatment efficacy between the 500 ppm and 1,500 ppm of Celecoxib, indicating a dose-dependent efficacy. Conclusions: Celecoxib is effective in delaying onset of early lesions induced by DMBA and in slowing growth of the tumors in hamster cheek pouches during the postinitiation stage. Its treatment efficacy appears to be dose dependent. [source]

P53 and Ki-67 as Outcome Predictors for Advanced Squamous Cell Cancers of the Head and Neck Treated With Chemoradiotherapy,

THE LARYNGOSCOPE, Issue 11 2001
Pierre Lavertu MD
Abstract Hypothesis P53 and Ki-67 status will predict response to treatment, organ preservation, and survival in patients with advanced squamous cell cancers of the head and neck treated with chemoradiotherapy (CRT). Study Design Retrospective analysis of p53 and Ki-67 status from the CRT arm of a randomized, controlled trial (n = 50) and from patients receiving the same treatment but not enrolled in the trial (n = 55). Methods P53 and Ki-67 status were established from archived tissue samples using immunohistochemical (IHC) staining. Tumors were positive for p53 (p53+) when more than 2% of cells stained for p53 and were positive for Ki-67 (Ki-67+) when any cell stained for Ki-67. End points were tumor response, tumor recurrence, survival status, and organ preservation at last follow-up, and time to events. Predictive models were calculated for each outcome. Results Neither marker predicted tumor response to treatment. P53+ status was associated with tumor recurrence (P = .003) and locoregional recurrence (P = .003). Adjusting for time to event, p53+ status was significantly related to a lower recurrence-free survival (P = .004), lower disease-specific survival (P = .04), lower overall survival with primary site preservation (P = .03), and lower disease-specific survival with primary site preservation (P = .003). Multivariate analysis revealed that p53+ status was significantly related to a lower recurrence-free survival (P = .01, risk ratio [RR] = 3.65) and lower disease-specific survival with organ preservation (P = .02, RR = 3.41). Ki-67+ status was not related to any variables. However, multivariate analysis revealed that Ki-67+ was significantly related to a lower overall survival (P = .05, RR = 2.03). The combination of both markers negative (p53-/Ki-67-) was associated with a lower incidence of tumor recurrence (P = .02), lower locoregional recurrence (P = .01), and fewer second primary lesions (P = .04). Adjusting for time to event, p53-/Ki-67- status was significantly related to a higher recurrence-free survival (P = .02), higher disease-specific survival with primary site preservation (P = .02), and higher overall survival with primary site preservation (P = .02). Multivariate analysis revealed that p53-/Ki-67- status was significantly related to a higher overall survival with site preservation (P = .01, RR = 2.78). Conclusions P53 and Ki-67 status appear to be related to the various survival end points considered in this study. However, this relation does not seem to be sufficient to warrant treatment modifications. Closer follow-up may be justified in both p53+ and Ki67+ patients to detect recurrence or a second primary at an earlier stage, possibly improving survival. [source]

No Evidence for Microsatellite Instability in Immunodeficiency-Related Skin Cancers

AMERICAN JOURNAL OF TRANSPLANTATION, Issue 1 2010
C. Borie
No abstract is available for this article. [source]

The dielectric properties of cancerous tissues in a nude mouse xenograft model

BIOELECTROMAGNETICS, Issue 7 2004
Done-Sik Yoo
Abstract The dielectric properties of various cancers, namely brain tumor, breast cancer, gastric carcinoma, and colon cancer, were measured in the frequency range of 500 MHz to 5 GHz. Cancers were cultivated applying the xenograft model of growing human cancerous tissues using the specific pathogen free, homo inbred mouse (a nude mouse). The complex permittivity was measured using an open-ended coaxial probe (HP85070B) and a computer controlled network analyzer (HP8510C). For the measurement of the dielectric properties, a total of 58 xenografted specimens was used. The results showed that measured values of complex permittivity for all four cancerous tissues were similar, with little variations over the frequency range used. It might be agreed that components and characteristics of different cancerous tissues would be similar despite their different occurrences in the human body. It is necessary to investigate this result further. Bioelectromagnetics 25:492,497, 2004. © 2004 Wiley-Liss, Inc. [source]

Prognostic significance of glycoprotein pMQ1 in breast cancer,

BRITISH JOURNAL OF SURGERY (NOW INCLUDES EUROPEAN JOURNAL OF SURGERY), Issue 3 2006
L. J. Fon
Background: A novel glycoprotein, pMQ1, is positively correlated with increasing histological grade in malignant astrocytomas. Cerebral metastases from breast cancer have also been found to contain pMQ1-positive cells. This study aimed to determine the role of pMQ1 in primary breast cancer. Methods: Breast cancer specimens were analysed for pMQ1 by immunohistochemistry. The expression of pMQ1 was correlated with conventional prognostic indicators. Kaplan,Meier analyses were performed to compare clinical outcome between pMQ1-positive and pMQ1-negative tumours. Results: pMQ1 was expressed in most of the breast cancer specimens. The surrounding normal tissue margins and benign breast tissues always lacked pMQ1 expression. A significant positive correlation was observed between pMQ1 expression and histological grade, the presence of lymphovascular invasion and Nottingham Prognostic Index. Cancers that were pMQ1 positive were significantly more likely to develop a local recurrence. Conclusion: pMQ1 appears to be a tumour-associated protein. The positive correlation of pMQ1 with histological grade, presence of lymphovascular invasion and Nottingham Prognostic Index suggests that it confers an adverse prognosis. Copyright © 2005 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd. [source]

Epidemiological study of oesophageal and gastric cancer in south-east England,

BRITISH JOURNAL OF SURGERY (NOW INCLUDES EUROPEAN JOURNAL OF SURGERY), Issue 9 2001
Mr H. M. Kocher
Background: This epidemiological study was carried out to establish the magnitude of the changing incidence of gastric and oesophageal cancer. Methods: Time-trend analyses of subsite-specific cancers of the oesophagus and stomach were performed using data from the Thames Cancer Registry database (1960,1996) for the South Thames Region. The changes in sex ratio and peak age of incidence are reported. Results: In the upper two-thirds of the oesophagus there was no significant change in the incidence rate, but the lower third of the oesophagus showed a marked rise for both sexes (average annual change +0·05 for men, +0·009 for women). For the gastric cardia, the incidence in males increased (average annual change +0·025), while in females it remained unchanged. Cancers of the oesophagogastric junction showed a clear increase for both sexes (average annual change +0·07 for men, +0·009 for women). There were changes in the sex ratio and peak age of incidence for all subsite cancers for both sexes. Conclusion: Over a 37-year period the incidence of cancer of the oesophagogastric junction increased threefold, while the incidence of cancers of the other subsites of the stomach decreased. Further studies are needed to investigate the aetiology of these changes. © 2001 British Journal of Surgery Society Ltd [source]

Black-White Mortality Disparities Increasing for Some Cancers

CA: A CANCER JOURNAL FOR CLINICIANS, Issue 2 2009
Mary Desmond Pinkowish News & Views Editor
No abstract is available for this article. [source]

2004 Surgeon General's Report Links More Cancers to Smoking

CA: A CANCER JOURNAL FOR CLINICIANS, Issue 5 2004
Article first published online: 31 DEC 200
No abstract is available for this article. [source]