Cancer In Conjunction Research Articles

Deoxycholate, an endogenous cytotoxin/genotoxin, induces the autophagic stress-survival pathway: implications for colon carcinogenesis.

We report that deoxycholate (DOC), a hydrophobic bile acid associated with a high-fat diet, activates the autophagic pathway in non-cancer colon epithelial cells (NCM-460), and that this activation contributes to cell survival. The DOC-induced increase in autophagy was documented by an increase in autophagic vacuoles (detected using transmission electron microscopy, increased levels of LC3-I and LC3-II (western blotting), an increase in acidic vesicles (fluorescence spectroscopy of monodansycadaverine and lysotracker red probes), and increased expression of the autophagic protein, beclin-1 (immunohistochemistry/western blotting). The DOC-induced increase in beclin-1 expression was ROS-dependent. Rapamycin (activator of autophagy) pre-treatment of NCM-460 cells significantly (P < .05) decreased, and 3-MA (inhibitor of autophagy) significantly (P < .05) increased the cell loss caused by DOC treatment, alone. Rapamycin pre-treatment of the apoptosis-resistant colon cancer cell line, HCT-116RC (developed in our laboratory), resulted in a significant decrease in DOC-induced cell death. Bafilomycin A1 and hydroxychloroquine (inhibitors of the autophagic process) increased the DOC-induced percentage of apoptotic cells in HCT-116RC cells. It was concluded that the activation of autophagy by DOC has important implications for colon carcinogenesis and for the treatment of colon cancer in conjunction with commonly used chemotherapeutic agents.

Alcohol Drinking and One-Carbon Metabolism-Related Gene Polymorphisms on Pancreatic Cancer Risk

Effect of alcohol consumption on pancreatic cancer risk has been investigated in many studies, but results have been inconsistent. We conducted a case-control study to assess the effect of alcohol on pancreatic cancer in conjunction with polymorphisms in one-carbon metabolism enzymes, methylenetetrahydrofolate reductase (MTHFR C677T), methionine synthase (MTR A2756G), methionine synthase reductase (MTRR A66G), and thymidylate synthase (TS) variable number of tandem repeat. A total of 157 pancreatic cancer patients and 785 age- and sex- matched control subjects were genotyped for polymorphisms. Odds ratios (OR) with 95% confidence intervals (95% CI) were estimated using unconditional logistic models adjusted for potential confounders. Heavy alcohol drinking was marginally associated with an increased risk of pancreatic cancer (OR, 1.90; 95% CI, 1.00-3.62). None of the polymorphisms showed any significant effect on pancreatic cancer risk by genotype alone. In stratified analysis, effect of alcohol consumption on pancreatic cancer was observed in individuals with the MTHFR 667 CC, MTR 2756 AA, or MTRR 66 G allele. OR (95% CI) of pancreatic cancer for heavy drinkers compared with never drinkers was 4.50 (1.44-14.05) in the MTHFR 667 CC genotype, 2.65 (1.17-6.00) in the MTR 2756 AA genotype, and 3.35 (1.34-8.36) in the MTRR 66 G allele carriers. These results suggest that the folate-related enzyme polymorphism modifies the association between drinking habit and pancreatic cancer risk.

Using model checking for critiquing based on clinical guidelines

Medical critiquing systems compare clinical actions performed by a physician with a predefined set of actions. In order to provide useful feedback, an important task is to find differences between the actual actions and a set of 'ideal' actions as described by a clinical guideline. In case differences exist, the critiquing system provides insight into the extent to which they are compatible. We propose a computational method for such critiquing, where the ideal actions are given by a formal model of a clinical guideline, and where the actual actions are derived from real world patient data. We employ model checking to investigate whether a part of the actual treatment is consistent with the guideline. We show how critiquing can be cast in terms of temporal logic, and what can be achieved by using model checking. Furthermore, a method is introduced for off-line computing relevant information which can be exploited during critiquing. The method has been applied to a clinical guideline of breast cancer in conjunction with breast cancer patient data.

Pyometra presenting in conjunction with bowel cancer in a post-menopausal women: a case report

This case describes a 71 year old, post-menopausal woman who developed vaginal discharge. This complaint ultimately led to the discovery of bowel cancer in conjunction with a large sterile pyometra.The pyometra was not due to genital malignancy. The most likely conclusion is that the pyometra may have arisen as an inflammatory response to the adjacent bowel pathology. This case report highlights the need for clinicians to consider non-gynaecological cancer as a possible cause for otherwise unexplained pyometra.

A New Angiogenesis Inhibitor

Although antibodies directed against vascular endothelial growth factor (αVEGF) can prolong life when given to individuals with certain cancers in conjunction with chemotherapy, inhibition of VEGF signaling can elicit adverse effects and also stimulate the production of alternative angiogenic mechanisms in tumors (see Jain and Xu). Noting that placental growth factor [PIGF, a member of the VEGF family that binds VEGF receptor 1 (VEGFR-1)] is not required for normal development and maintenance of the vasculature but has been implicated in pathological angiogenesis, Fischer et al . investigated the effect on tumors of an antibody directed against PIGF (αPIGF). αPIGF inhibited the growth or metastasis or both of various tumors in mice, some of which were resistant to inhibition of VEGFR signaling. Furthermore, αPIGF enhanced inhibition of tumor growth by the chemotherapeutic agents gemcitabine and cyclophosphamide, as well as the anticancer effects of an antibody directed against VEGFR-2 (αVEGFR-2). αPIGF inhibited tumor angiogenesis and lymphangiogenesis, as well as tumor recruitment of proangiogenic macrophages. αPIGF failed to increase the expression of several proangiogenic genes stimulated by αVEGFR-2, and it neither mimicked nor enhanced αVEGFR-2-dependent side effects. Indeed, pregnant mice treated with αPIGF delivered litters of healthy pups. Thus, the authors hope that αPIGF might represent a useful addition to the current anticancer armamentarium. C. Fischer, B. Jonckx, M. Mazzone, S. Zacchigna, S. Loges, L. Pattarini, E. Chorianopoulos, L. Liesenborghs, M. Koch, M. De Mol, M. Autiero, S. Wyns, S. Plaisance, L. Moons, N. van Rooijen, M. Giacca, J.-M. Stassen, M. Dewerchin, D. Collen, P. Carmeliet, Anti-PIGF inhibits growth of VEGF(R)-inhibitor-resistant tumors without affecting healthy vessels. Cell 131 , 463-475 (2007). [PubMed] R. K. Jain, L. Xu, αPlGF: A new kid on the antiangiogenesis block. Cell 131 , 443-445 (2007). [PubMed]

Inhibitory effect of meloxicam, a selective cyclooxygenase‐2 inhibitor, and ciglitazone, a peroxisome proliferator‐activated receptor gamma ligand, on the growth of human ovarian cancers

It was recently reported that high expression of peroxisome proliferator-activated receptor gamma (PPARgamma) and low expression of cyclooxygenase-2 (COX-2) might be involved in the inhibition of ovarian tumor progression and confirmed that PPARgamma activation could suppress COX-2 expression via the nuclear factor-kappaB pathway in ovarian cancer cells. The current study investigated whether meloxicam, a selective COX-2 inhibitor, and ciglitazone, a ligand for PPARgamma, inhibit the growth of human ovarian cancer cell lines and aimed to elucidate the molecular mechanism of their antitumor effect. Tumor growth and survival were examined in female nu/nu mice xenografted with subcutaneous OVCAR-3 tumors or with intraperitoneal DISS tumors and treated with meloxicam (162 ppm in diet, every day) or ciglitazone (15 mg/kg intraperitoneally once a week). Both meloxicam and ciglitazone treatments significantly suppressed the growth of OVCAR-3 tumors xenotransplanted subcutaneously and significantly prolonged the survival of mice with malignant ascites derived from DISS cells as compared with controls. Meloxicam treatment decreased COX-2 expression in tumors by 2.5-fold compared with that observed in untreated tumors. Although ciglitazone treatment did not alter COX-2 expression in tumors, it reduced the expression of microsomal prostaglandin (PG) E synthase, which converts COX-derived PGH(2) to PGE(2). Both meloxicam and ciglitazone decreased PGE(2) levels in serum as well as in ascites. Reduced microvessel density and induced apoptosis were found in solid OVCAR-3 tumors treated with either meloxicam or ciglitazone. These results indicate that both meloxicam and ciglitazone produce antitumor effects against ovarian cancer in conjunction with reduced angiogenesis and induction of apoptosis.

Clofibric acid, a peroxisome proliferator–activated receptor α ligand, inhibits growth of human ovarian cancer

Recent reports have shown that peroxisome proliferator-activated receptor (PPAR)alpha ligands reduce growth of some types of malignant tumors and prevent carcinogenesis. In this study, we investigated the inhibitory effect of clofibric acid (CA), a ligand for PPARalpha on growth of ovarian malignancy, in in vivo and in vitro experiments using OVCAR-3 and DISS cells derived from human ovarian cancer and aimed to elucidate the molecular mechanism of its antitumor effect. CA treatment significantly suppressed the growth of OVCAR-3 tumors xenotransplanted s.c. and significantly prolonged the survival of mice with malignant ascites derived from DISS cells as compared with control. CA also dose-dependently inhibited cell proliferation of cultured cell lines. CA treatment increased the expression of carbonyl reductase (CR), which promotes the conversion of prostaglandin E(2) (PGE(2)) to PGF(2alpha), in implanted OVCAR-3 tumors as well as cultured cells. CA treatment decreased PGE(2) level as well as vascular endothelial growth factor (VEGF) amount in both of OVCAR-3-tumor and DISS-derived ascites. Reduced microvessel density and induced apoptosis were found in solid OVCAR-3 tumors treated by CA. Transfection of CR expression vector into mouse ovarian cancer cells showed significant reduction of PGE(2) level as well as VEGF expression. These results indicate that CA produces potent antitumor effects against ovarian cancer in conjunction with a reduction of angiogenesis and induction of apoptosis. We conclude that CA could be an effective agent in ovarian cancer and should be tested alone and in combination with other anticancer drugs.

Associations between vitamin D, vitamin D receptor gene and the androgen receptor gene with colon and rectal cancer

The transcriptional activity of the vitamin D receptor (VDR) gene is regulated, at least in part, by the androgen receptor (AR) gene. We evaluate how the number of polyglutamine (CAG) repeats of the AR gene influence colorectal cancer in conjunction with vitamin D, sunshine exposure and VDR. Studies of colon (1,580 cases and 1,968 controls) and rectal (797 cases and 1,016 controls) cancer were used. Vitamin D intake and average hours of sunshine exposure interacted with AR genotype in men. Men with low vitamin D intake or low levels of sunshine exposure who had 23+ CAG repeats of the AR gene had the greatest risk of colon cancer. ORs for men with 23 or more CAG repeats of the AR gene and in the lowest tertile of vitamin D intake or sunshine exposure were 1.71 (95% CI 1.14, 2.56) and 1.51 (95% CI 1.09, 2.09). Men with high levels of sunshine exposure were at reduced risk of developing rectal cancer if they had 23 or more CAG repeats (OR 0.62 95% CI 0.39, 0.97) than if they had fewer than 23 CAG repeats. The FF genotype of the Fok1 VDR gene was associated with reduced risk of colon cancer among women with any allele of 23+ CAG repeats (OR 0.62 95% CI 0.44, 0.88), whereas men with the LL/bb VDR genotypes were at reduced risk of rectal cancer if they also had 23+ CAG repeats (OR 0.71 95% CI 0.48, 1.05) relative to men with fewer than 23 CAG repeats of the AR gene. These data provide support for the role of vitamin D and sunshine exposure in the etiology of colorectal cancer and suggest that AR gene may modulate the association.

Conserving fertility in the management of gynaecological cancers

The quality of cancer treatment is judged by both morbidity and mortality. Patients benefit if morbidity is reduced without compromising mortality. This applies particularly for women who develop gynaecological malignancy during their childbearing years where curative treatment also renders them infertile. This study reviews the increasing role of fertility-sparing surgery in such women. A literature search was undertaken using PubMed, entering the terms endometrial cancer, cervical cancer and ovarian cancer in conjunction with the terms fertility and fertility sparing. Each relevant identified paper was reviewed, references checked and results collated to provide an evidence-based summary of fertility-sparing treatments for gynaecological malignancy. Fertility-sparing surgery is appropriate in many circumstances, and all doctors who advise young women with gynaecological malignancy should be aware of these possibilities. However, data are relatively sparse in many situations, and careful counselling and balanced guidance are essential if patients are to understand the full implications of their choices.

931. Inhibition of VEGF Signaling Pathway and Tumor Metastasis

Top of pageAbstract Blocking vascular endothelial growth factor (VEGF) signaling pathway appears to be an effective approach to suppress tumor angiogenesis and metastasis. Because degree of tumor malignancy correlates with the expression of VEGF and the inverse expression of tumor suppressor gene p16, we examined whether restoration of wild-type p16 in cancer cells that lack p16 expression would modulate VEGF expression, and if so, how is the effect of p16 expression on tumor angiogenesis and metastasis. Human breast cancer cell lines MDA-MB-231, MCF-7 and mouse breast cancer cell line JygMC(A) were used as models for this study. To facilitate induction of p16 expression, a replication-defective recombinant adenovirus expressing human wild-type p16 (AdRSVp16) has been generated. Our study showed that adenoviral-mediated p16 expression downregulated VEGF expression at both mRNA and protein levels in breast cancer cells, as well as VEGF receptor activation. By using a chimeric VEGF promoter-reporter gene construct, we demonstrated that p16 downregulated VEGF gene expression at the transcriptional level. A molecular mechanism of how p16 modulates VEGF expression at the transcriptional level is proposed. By comparing with control virus-treated group, AdRSVp16 inhibited breast cancer angiogenesis in dorsal air sac and matrigel plug models, in vitro and in vivo growth of breast cancer cells, and metastasis in a subcutaneous metastasis model. The dual effects of p16's anti-proliferation and anti-angiogenesis were examined by simultaneously analyzing proliferation marker PCNA and neovascularization marker CD31 (immunohistochemistry), and apoptosis (TUNEL) inside the tumors. Our results showed that p16 has combinative effects on breast tumor angiogenesis and proliferation. Taken together, these results demonstrate that p16 downregulates VEGF gene expression at the transcriptional level, inhibits angiogenesis, and suppresses tumor growth and metastasis in breast cancer cells. This study suggests that viral vector-based p16 gene therapy may have a clinical potential to treat breast cancer in conjunction with other therapeutic modalities.

The rationale for combined chemo/immunotherapy using a Toll-like receptor 3 (TLR3) agonist and tumour-derived exosomes in advanced ovarian cancer

A clinical trial employing an immunotherapeutic approach based on the use of a Toll-like receptor 3 (TLR3) agonist and tumour-derived exosomes carrying tumour-associated antigens is planned in advanced ovarian cancer in conjunction with conventional first line chemotherapy. Most patients with ovarian cancer present with advanced disease and despite high initial response rate to chemotherapy the majority will relapse within 2 years with poor overall survival. Tumour antigen-specific T cells are naturally occurring in ovarian cancer patients and T cell infiltration of the tumour is highly prognostic. Novel immunotherapy to expand and activate tumour antigen-specific T cells combined with adjuvant treatment to overcome tumour-induced immunosuppression is considered to be therapeutically beneficial. The rationale for adopting such a combined approach is discussed here.

P12CDK2-AP1 mediates DNA damage responses induced by cisplatin

We examined the biological role of p12(CDK2-AP1) in cisplatin-mediated responses by using murine ES p12(CDK2-AP1) knockout clones generated by a targeted disruption of murine p12(CDK2-AP1). Homozygous knockout clones showed an increased cellular proliferation along with an increase in S and a decrease in G2/M phase populations. Interestingly, ES p12(CDK2-AP1) knockout clones showed a resistance to cisplatin treatment along with an increased DNA repair activity assessed by host cell reactivation assay using a cisplatin-damaged reporter DNA and a significant reduction of apoptosis upon cisplatin treatment. By using stable p12(CDK2-AP1) short interfering RNA (siRNA) clones from human normal oral keratinocytes, we confirmed that downregulation of p12(CDK2-AP1) resulted in a resistance to cisplatin. More interestingly, cisplatin treatment resulted in a reduction of CDK2 kinase activity in control clones, but p12(CDK2-AP1) knockout clones showed a sustained CDK2 kinase activity. These data suggest that p12(CDK2-AP1) plays a role in cisplatin-mediated cellular responses by modulating CDK2 activity. These data further suggest p12(CDK2-AP1) is a potential gene therapeutic agent for oral/head and neck cancer in conjunction with DNA-damaging agents such as cisplatin.

Catheter-based ultrasound applicators for selective thermal ablation: progress towards MRI-guided applications in prostate

High-temperature thermal therapy is emerging as a feasible treatment option for prostate cancer and benign prostatic hyperplasia. Previous investigations have demonstrated distinct advantages of catheter-based ultrasound technology over other heating modalities for thermal ablation therapies, with significant potential for better spatial control and faster heating times. The purpose of this study was to develop ultrasound devices and techniques specifically for treating prostate cancer in conjunction with magnetic resonance thermal imaging (MRTI) to monitor and control treatment progression. Directional transurethral applicators have been designed with arrays of sectored tubular (90° active acoustic sector) or with narrow planar transducer segments and integrated with a flexible delivery catheter with a cooling balloon. This applicator can be rotated within the prostatic urethra to target specific regions during treatment. MRI compatible catheter-cooled interstitial ultrasound applicators with 180° active acoustic sectors were developed specifically to treat the prostate. These applicators may be implanted through the perineum into the posterior portion of the prostate, with their heating energy directed away from the rectum. Both heating strategies were evaluated via biothermal simulations and in vivo experiments within canine prostate (n = 3). During the in vivo studies, MRTI was used to monitor treatment temperatures, cytotoxic thermal doses (t43>240 min) and corresponding maximum temperature thresholds (Tmax>52°C) within three imaging planes simultaneously. Urethral and endorectal cooling was employed with both treatment strategies to provide further protection of the urethral mucosa and rectum from thermal damage. Results using the transurethral applicators demonstrated that narrow zones of coagulation (∼30° sector for planar, ∼90° for tubular), extending up to 20 mm from the urethra to the periphery of the prostate gland, could be produced within 10–15 min. Further, rotation of the applicator during treatment could be used to destroy larger regions in the prostate. Experiments using multiple interstitial directional applicators (∼180° active sectors), implanted within the posterior margin of the prostate with the energy directed away from the rectum, produced contiguous zones of thermal coagulation which extended from the posterior prostate toward the anterior-lateral periphery of the gland. Both transurethral and interstitial treatment strategies demonstrated significant potential for thermal ablation of localized prostate cancer, particularly when MRTI is used to guide and assess treatment.

Endocrine cancers and second primary tumors

Purpose To explore etiologic clues for endocrine cancers by evaluating risk of multiple cancers in conjunction with thyroid and adrenal cancer. Methods We conducted cohort studies including all 2-month survivors of thyroid and adrenal cancer (excluding neuroblastoma) in the U.S. Surveillance, Epidemiology and End Results (SEER) cancer registries program (1973–2000). Relative risks are expressed as the ratio of observed (O) to expected (E) number of cases. Absolute excess risks (EAR) are expressed as the difference between O and E, divided by the person-years (PY) at risk, and then expressed per 10,000 PY. Results Among 29,456 thyroid cancer survivors, 2214 developed a second cancer (O/E = 1.11, 95% CI = 1.06–1.15, EAR = 7.47/10,000 PY), with the highest risk seen in the first year (26%). Patients less than 40 years at diagnosis of thyroid cancer had a 39% increased risk; older patients had a 6% increased risk. We observed a likely radiotherapy-related excess of leukemia. Consistently increased risks also were observed for cancers of the breast, prostate, and kidney; a decreased risk was observed for lung cancer. Based on small numbers of cases, cancers of the salivary glands, trachea, scrotum, adrenal glands, and brain or CNS occurred in excess. Among 811 survivors of adrenal cancer, a 1.76-fold (95% CI = 1.33–2.27) risk of second cancers was observed (O = 57, EAR = 71.36/10,000 PY). Following adrenal carcinoma excesses, were observed for lung, bladder, and prostate cancer; kidney cancer occurred in excess after pheochromocytoma. Young carcinoma patients ( Conclusion Thyroid cancer survivors are at moderately increased risk of second cancers of many different organs. Enhanced clinical surveillance, radiotherapy, and hormonal and genetic factors likely play a role. Survivors of adrenal carcinoma are at increased risk of cancers of the lung, bladder, and prostate. Second cancer risks among young patients suggest Li–Fraumeni syndrome.

PKB/Akt phosphorylates p27, impairs nuclear import of p27 and opposes p27-mediated G1 arrest.

Mechanisms linking mitogenic and growth inhibitory cytokine signaling and the cell cycle have not been fully elucidated in either cancer or in normal cells. Here we show that activation of protein kinase B (PKB)/Akt, contributes to resistance to antiproliferative signals and breast cancer progression in part by impairing the nuclear import and action of p27. Akt transfection caused cytoplasmic p27 accumulation and resistance to cytokine-mediated G1 arrest. The nuclear localization signal of p27 contains an Akt consensus site at threonine 157, and p27 phosphorylation by Akt impaired its nuclear import in vitro. Akt phosphorylated wild-type p27 but not p27T157A. In cells transfected with constitutively active Akt(T308DS473D)(PKB(DD)), p27WT mislocalized to the cytoplasm, but p27T157A was nuclear. In cells with activated Akt, p27WT failed to cause G1 arrest, while the antiproliferative effect of p27T157A was not impaired. Cytoplasmic p27 was seen in 41% (52 of 128) of primary human breast cancers in conjunction with Akt activation and was correlated with a poor patient prognosis. Thus, we show a novel mechanism whereby Akt impairs p27 function that is associated with an aggressive phenotype in human breast cancer.

Transcription-targeted gene therapy for androgen-independent prostate cancer.

The Escherichia coli enzyme (purine nucleoside phosphorylase, PNP) gene is delivered directly into PC3 tumors by one injection of replication-deficient human type-5 adenovirus (Ad5). Expressed PNP converts the systemically administered prodrug, 6MPDR, to a toxic purine, 6MP, causing cell death. We sought to increase the specificity of recombinant Ad vectors by controlling PNP expression with the promoter region from the androgen-dependent, prostate-specific rat probasin (Pb) gene. To increase its activity, the promoter was combined with the SV40 enhancer (SVPb). Cell lines were transfected with plasmids containing both a reporter gene, under SVPb control, and a reference gene cassette to allow normalization of expression levels. Plasmids expressed approximately 20-fold more reporter in prostate cancer than in other cells, but surprisingly, the SVPb element was both androgen-independent and retained substantial prostate specificity. Killing by Ad5-SVPb-PNP vector of cell lines cultured with 6MPDR for 6 days was 5- to 10-fold greater in prostate cancer than in liver or lung cells. In vivo, a single intratumoral injection of Ad5-SVPb-PNP (4 x 10(8) pfu), followed by 6MPDR administration twice daily for 6 days, significantly suppressed the growth of human prostate tumors in nude mice and increased their survival compared to control animals. Thus, the androgen-independent, prostate-targeting Ad5 vector reduces human prostate cancer growth significantly in vitro and in vivo. This first example of an androgen-independent vector points the way toward treatment of emerging androgen-independent prostate cancer in conjunction with hormone ablation therapy at a time when the tumor burden is low.

The physiology, medical management and oral implications of menopause

Approximately 36 million women in the United States are in the postmenopausal phase of life. The vast majority of these women experienced spontaneous cessation of menses between the ages of 47 and 55 years when the production of estrogen decreased because of an inadequate number of functioning follicles within their ovaries. Fewer women entered menopause after surgical removal of both ovaries. This procedure usually is performed prophylactically to prevent ovarian cancer in conjunction with a hysterectomy, which is required to treat abnormal bleeding, endometriosis or pelvic inflammatory disease. The physiological changes associated with spontaneous or surgical menopause cause some women to experience uncomfortable symptoms such as hot flashes, night sweats and vaginal dryness. In addition, estrogen deprivation arising from menopause in association with age-related factors disproportionately increases the risk of developing cardiovascular disease (that is, myocardial infarct, stroke), osteoporosis, Alzheimer's disease and oral disease. Hormone replacement therapy, or HRT (estrogen or estrogen and progestin), often is prescribed on a short-term basis to alleviate the uncomfortable symptoms associated with estrogen deficiency and on a long-term basis to prevent some of the chronic illnesses common to postmenopausal women. Dentists who treat women entering menopause need to consider the stressful phase of life their patients are experiencing. Clinical findings of postmenopausal problems on dental examination may include a paucity of saliva, increased dental caries, dysesthesia, taste alterations, atrophic gingivitis, periodontitis and osteoporotic jaws unsuitable for conventional prosthetic devices or dental implants. Panoramic dental radiographs may reveal calcified carotid artery atheromas. Dentists have an opportunity to refer women who are not under the care of a gynecologist for an evaluation to determine the appropriateness of HRT for its systemic and oral health benefits.

RADIOLOGICAL QUIZ

The precise roles of fiberoptic bronchoscopy (FOB) and computed tomography (CT) of the chest in the evaluation of patients presenting with hemoptysis have not been clearly defined. On the assumption that both procedures would likely provide unique and complementary information, a prospective study with blinded interpreters using a modified high-resolution CT technique (HRCT) and FOB was designed to evaluate 57 consecutive patients admitted to Bellevue Hospital with hemoptysis. Etiologies included bronchiectasis (25 percent), tuberculosis (16 percent), lung cancer (12 percent), aspergilloma (12 percent), and bronchitis (5 percent): in an additional 5 percent of cases, hemoptysis proved to be due miscellaneous causes, while in 19 percent hemoptysis proved to be cryptogenic. Patients with lung cancer all were at least 50 years old, smoked an average of 78 pack-years, and had less severe hemoptysis but of longer duration. All had conditions diagnosed both by HRCT and FOB. High-resolution CT proved of particular value in diagnosing bronchiectasis and aspergillomas, while FOB was diagnostic of bronchitis and mucosal lesions such as Kaposi's sarcoma. Fiberoptic bronchoscopy localized bleeding in only 51 percent of cases. The high sensitivity of CT in identifying both the intraluminal and extraluminal extent of central lung cancers in conjunction with its value in diagnosing bronchiectasis suggest that CT should be obtained prior to bronchoscopy in all patients presenting with hemoptysis.

Hemoptysis: Prospective High-Resolution CT/Bronchoscopic Correlation

The precise roles of fiberoptic bronchoscopy (FOB) and computed tomography (CT) of the chest in the evaluation of patients presenting with hemoptysis have not been clearly defined. On the assumption that both procedures would likely provide unique and complementary information, a prospective study with blinded interpreters using a modified high-resolution CT technique (HRCT) and FOB was designed to evaluate 57 consecutive patients admitted to Bellevue Hospital with hemoptysis. Etiologies included bronchiectasis (25 percent), tuberculosis (16 percent), lung cancer (12 percent), aspergilloma (12 percent), and bronchitis (5 percent): in an additional 5 percent of cases, hemoptysis proved to be due miscellaneous causes, while in 19 percent hemoptysis proved to be cryptogenic. Patients with lung cancer all were at least 50 years old, smoked an average of 78 pack-years, and had less severe hemoptysis but of longer duration. All had conditions diagnosed both by HRCT and FOB. High-resolution CT proved of particular value in diagnosing bronchiectasis and aspergillomas, while FOB was diagnostic of bronchitis and mucosal lesions such as Kaposi's sarcoma. Fiberoptic bronchoscopy localized bleeding in only 51 percent of cases. The high sensitivity of CT in identifying both the intraluminal and extraluminal extent of central lung cancers in conjunction with its value in diagnosing bronchiectasis suggest that CT should be obtained prior to bronchoscopy in all patients presenting with hemoptysis.

The effect of therapeutic drugs used in inflammatory bowel disease on the incidence and growth of colonic cancer in the dimethylhydrazine rat model.

An increased incidence of colonic cancer is associated with chronic inflammatory bowel disease. Sulphasalazine, metronidazole and more recently, modified forms of 5-aminosalicylic acid are used for maintenance therapy of inflammatory bowel disease. In a series of experiments, we used the 1,2-dimethylhydrazine animal model of colonic cancer in conjunction with these drugs, to study the effect on the development of colon cancer. Inbred male Wistar rats were divided into groups receiving orally: metronidazole 18 mg Kg-1 dy-1; sulphasalazine 60 mg Kg-1 dy-1; 5-aminosalicylic acid 30 and 60 mg Kg-1 dy-1 and olsalazine 60 mg Kg-1 dy-1 administered daily. Half of each group also received weekly injections of DMH 40 mg Kg-1. Metronidazole, sulphasalazine and 30 mg Kg-1 dy-1 5-aminosalicylic acid were co-carcinogenic, increasing either the number of cancers or tumour size. In contrast 60 mg Kg-1 dy-1 5-aminosalicylic acid inhibited tumour size and olsalazine had no effect. These results may have a bearing on long term maintenance therapy in inflammatory bowel disease.