OBJECTIVES: Colorectal cancer (CRC) is the third most common cancer and the fourth most common cause of cancer death in the world. The aim of this study was to investigate the provincial distribution of the incidence of CRC across Iran. METHODS: This epidemiologic study used data from the National Cancer Registry of Iran and the Center for Disease Control and Prevention of the Ministry of Health and Medical Education of Iran. The average annual age-standardized rate (ASR) for the incidence of CRC was calculated for each province. RESULTS: We found that adenocarcinoma (not otherwise specified) was the most common histological subtype of CRC in males and females, accounting for 81.91 and 81.95% of CRC cases, respectively. Signet ring cell carcinoma was the least prevalent subtype of CRC in males and females and accounted for 1.5 and 0.94% of CRC cases, respectively. In patients aged 45 years or older, there was a steady upward trend in the incidence of CRC, and the highest ASR of CRC incidence among both males and females was in the age group of 80-84 years, with an ASR of 144.69 per 100,000 person-years for males and 119.18 per 100,000 person-years for females. The highest incidence rates of CRC in Iran were found in the central, northern, and western provinces. Provinces in the southeast of Iran had the lowest incidence rates of CRC. CONCLUSIONS: Wide geographical variation was found in the incidence of CRC across the 31 provinces of Iran. These variations must be considered for prevention and control programs for CRC, as well as for resource allocation purposes.
Adenocarcinoma ; Carcinoma, Signet Ring Cell ; Centers for Disease Control and Prevention (U.S.) ; Colorectal Neoplasms* ; Education, Medical ; Epidemiologic Studies ; Female ; Humans ; Incidence* ; Iran* ; Male ; Resource Allocation

OBJECTIVES: Colorectal cancer (CRC) is the third most common cancer and the fourth most common cause of cancer death in the world. The aim of this study was to investigate the provincial distribution of the incidence of CRC across Iran.METHODS: This epidemiologic study used data from the National Cancer Registry of Iran and the Center for Disease Control and Prevention of the Ministry of Health and Medical Education of Iran. The average annual age-standardized rate (ASR) for the incidence of CRC was calculated for each province.RESULTS: We found that adenocarcinoma (not otherwise specified) was the most common histological subtype of CRC in males and females, accounting for 81.91 and 81.95% of CRC cases, respectively. Signet ring cell carcinoma was the least prevalent subtype of CRC in males and females and accounted for 1.5 and 0.94% of CRC cases, respectively. In patients aged 45 years or older, there was a steady upward trend in the incidence of CRC, and the highest ASR of CRC incidence among both males and females was in the age group of 80-84 years, with an ASR of 144.69 per 100,000 person-years for males and 119.18 per 100,000 person-years for females. The highest incidence rates of CRC in Iran were found in the central, northern, and western provinces. Provinces in the southeast of Iran had the lowest incidence rates of CRC.CONCLUSIONS: Wide geographical variation was found in the incidence of CRC across the 31 provinces of Iran. These variations must be considered for prevention and control programs for CRC, as well as for resource allocation purposes.
Adenocarcinoma ; Carcinoma, Signet Ring Cell ; Centers for Disease Control and Prevention (U.S.) ; Colorectal Neoplasms ; Education, Medical ; Epidemiologic Studies ; Female ; Humans ; Incidence ; Iran ; Male ; Resource Allocation

Clear cell carcinoma (CCC) of the ovary is known to show poorer sensitivity to chemotherapeutic agents and to be associated with a worse prognosis than the more common serous adenocarcinoma or endometrioid adenocarcinoma. To improve the survival of patients with ovarian CCC, the deeper understanding of the mechanism of CCC carcinogenesis as well as the efforts to develop novel treatment strategies in the setting of both front-line treatment and salvage treatment for recurrent disease are needed. In this presentation, we first summarize the mechanism responsible for carcinogenesis. Then, we highlight the promising therapeutic targets in ovarian CCC and provide information on the novel agents which inhibit these molecular targets. Moreover, we discuss on the cytotoxic anti-cancer agents that can be best combined with targeted agents in the treatment of ovarian CCC.
Adenocarcinoma, Clear Cell/drug therapy/*etiology/metabolism ; Antineoplastic Agents/therapeutic use ; Female ; Forecasting ; Humans ; Neoplasm Recurrence, Local/prevention & control ; Ovarian Neoplasms/drug therapy/*etiology/metabolism

PURPOSE: To determine whether statin use delays the development of castration-resistant prostate cancer (CRPC) in patients with metastatic prostate cancer treated with androgen deprivation therapy (ADT). MATERIALS AND METHODS: A total of 171 patients with metastatic prostate cancer at the time of diagnosis who were treated with ADT between January 1997 and December 2013 were retrospectively analyzed. The patients were classified into two groups: the nonstatin use group (A group) and the statin use group (B group). Multivariate analysis was performed on statin use and other factors considered likely to have an effect on the time to progression to CRPC. RESULTS: The mean patient age was 67.1+/-9.1 years, and the mean follow-up period was 52 months. The mean initial prostate-specific antigen (PSA) level was 537 ng/mL. Of the 171 patients, 125 (73%) were in group A and 46 (27%) were in group B. The time to progression to CRPC was 22.7 months in group A and 30.5 months in group B, and this difference was significant (p=0.032). Blood cholesterol and initial PSA levels did not differ significantly according to the time to progression to CRPC (p=0.288, p=0.198). Multivariate analysis using the Cox regression method showed that not having diabetes (p=0.037) and using a statin (p=0.045) significantly increased the odds ratio of a longer progression to CRPC. CONCLUSIONS: Statin use in metastatic prostate cancer patients appears to delay the progression to CRPC. Large-scale, long-term follow-up studies are needed to validate this finding.
Adenocarcinoma/drug therapy/*secondary ; Adult ; Aged ; Aged, 80 and over ; Androgen Antagonists/therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Body Mass Index ; Diabetes Mellitus/drug therapy ; Disease Progression ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/*therapeutic use ; Male ; Middle Aged ; Neoplasm Grading ; Prostatic Neoplasms, Castration-Resistant/drug therapy/*pathology/*prevention & control ; Protective Factors ; Retrospective Studies ; Survival Rate ; Time Factors

A 58-year-old female patient, diagnosed with adenocarcinoma of the lung, underwent percutaneous vertebroplasty at the L4 vertebral body due to painful spinal metastases. Because of deep venous thrombosis of the left femoral and iliac veins, an inferior vena cava filter had been placed before vertebroplasty. Bone cement migrated into the venous bloodstream and then was being trapped within the previously placed filter. This case illustrates that caval filter could capture the bone cement and prevent it from migrating to the pulmonary circulation.
Adenocarcinoma/secondary ; Bone Cements/*adverse effects ; Embolism/*etiology ; Female ; Humans ; Iliac Vein ; Lumbar Vertebrae/surgery ; Lung Neoplasms/pathology ; Middle Aged ; Pulmonary Embolism/prevention & control ; Spinal Neoplasms/secondary ; *Vena Cava Filters ; *Vena Cava, Inferior ; Venous Thrombosis/radiography ; Vertebroplasty/*adverse effects/methods

OBJECTIVETo study the feasibility of chemoprevention of esophageal adenocarcinoma by celecoxib, a selective cyclooxygenase-2(COX-2) inhibitor using a rat model.

METHODSRats were divided into 3 groups: model group, celecoxib group, and control group. The rat surgical model was established by performing a gastrojejunostomy plus an esophagojejunostomy 5 mm distal to the gastrojejunal anastomosis. Twenty-eight weeks after surgery, all the animals were sacrificed and the pathological changes in the esophagus were examined macroscopically. COX-2 expression was analyzed by immunohistochemistry. Prostaglandin E2(PGE2) level was measured by enzyme-linked immunosorbent assay(ELISA).

RESULTSThe incidence of Barrett's esophagus and esophageal adenocarcinoma in the model group was 84% and 57% respectively, significantly higher than those in the control group(P<0.01). The incidence of esophageal adenocarcinoma in the celecoxib-treated group was significantly lower than that in the model group(P<0.01), and no esophageal adenocarcinoma was detected in the control group. COX-2 expression was detected in 100% of reflux esophagitis, Barrett esophagus and esophageal adenocarcinoma, but not found in the normal tissue from the esophagus and the jejunum(P<0.01). The PGE2 level in the esophageal tissue in the model group was significantly higher than that in the control group(P<0.01). Rats in the celecoxib-treated group had significantly lower PGE2 level than that in the model group(P<0.01). The PGE2 levels were significantly higher in rats with cancer than those without cancer(P<0.01).

CONCLUSIONCelecoxib successfully prevents the development of esophageal adenocarcinoma in a rat surgical model with mixed reflux of acid and duodenal juice and significantly decreases the risk of Barrett esophagus developing esophageal adenocarcinoma. COX-2 maybe an effective selective target of chemoprevention for esophageal adenocarcinoma.

Adenocarcinoma ; prevention & control ; Animals ; Barrett Esophagus ; drug therapy ; Celecoxib ; Cyclooxygenase 2 Inhibitors ; therapeutic use ; Disease Models, Animal ; Esophageal Neoplasms ; prevention & control ; Male ; Pyrazoles ; therapeutic use ; Rats ; Rats, Sprague-Dawley ; Sulfonamides ; therapeutic use

OBJECTIVEThis experiment aims to study the anti-angiogenic ability of vinorelbine combined with cetuximab in vitro and in vivo.

METHODSHuman lung adenocarcinoma A549 cells were used as control group. Proliferation of human umbilical vein endothelial cells (HUVEC) was assessed by MTT assay. Furthermore, we used Transwell chambers, capillary tube formation and flow cytometry to observe the effects of vinorelbine combined with cetuximab on HUVEC migration, tube formation and cell apoptosis, respectively. In addition, the anti-angiogenic ability of the drugs was checked using chicken chorioallantoic membrane (CAM) model.

RESULTSThe inhibitory rate of HUVEC growth was 25.8%, 39.2%, 54.0% for vinorelbine at the concentration of 0.1 ng/ml, 0.4 ng/ml, and 0.8 ng/ml, respectively; that of 0.25 microg/ml cetuximab was 19.7%, and that of 0.1 ng/ml vinorelbine + 0.25 microg/ml cetuximab, 0.4 ng/ml vinorelbine + 0.25 microg/ml cetuximab and 0.8 ng/ml vinorelbine + 0.25 microg/ml cetuximab was 29.5%, 46.4%, 64.6%, respectively. The inhibitory rates of the drugs at the above mentioned combinations of migration and tube formation of HUVEC were 51.9%, 68.2%, 95.0%, respectively. The inhibitory rate of 0.1 ng/ml + 0.25 microg/ml cetuximab and 0.4 ng/ml vinorelbine + 0.25 microg/ml cetuximab on tube formation of HUVEC was 38.8% and 57.7%, respectively, showing a sub-additive effect, and that of combination of 0.8 ng/ml vinorelbine + 0.25 microg/ml cetuximab was 78.9%, showing a synergistic effect. In addition, the apoptotic rate of HUVEC induced by 0.8 ng/ml vinorelbine + 0.25 microg/ml cetuximab was 59.9%, showing a synergistic effect. The in vivo experiment also showed that the combination of the two drugs had a synergistic anti-angiogenic effect.

CONCLUSIONBoth low dose vinorelbine and cetuximab have an anti-angiogenic effect in vitro and in vivo, and the combination of the two drugs has sub-additive or synergistic inhibitory effect on angiogenesis.

Adenocarcinoma ; blood supply ; pathology ; Angiogenesis Inhibitors ; pharmacology ; Animals ; Antibodies, Monoclonal ; pharmacology ; Antibodies, Monoclonal, Humanized ; Antineoplastic Agents ; pharmacology ; Antineoplastic Agents, Phytogenic ; pharmacology ; Apoptosis ; drug effects ; Cell Line, Tumor ; Cell Movement ; drug effects ; Cell Proliferation ; drug effects ; Cells, Cultured ; Cetuximab ; Chick Embryo ; Drug Synergism ; Endothelial Cells ; cytology ; Humans ; Lung Neoplasms ; blood supply ; pathology ; Neovascularization, Pathologic ; prevention & control ; Umbilical Veins ; cytology ; Vinblastine ; analogs & derivatives ; pharmacology

During carcinogenesis, NF-kappaB mediates processes associated with deregulation of the normal control of proliferation, angiogenesis, and metastasis. Thus, suppression of NF-kappaB has been linked with chemoprevention of cancer. Accumulating findings reveal that heat shock protein 90 (HSP90) is a molecular chaperone and a component of the IkappaB kinase (IKK) complex that plays a central role in NF-kappaB activation. HSP90 also stabilizes key proteins involved in cell cycle control and apoptosis signaling. We have determined whether the exogenous administration of isoflavone-deprived soy peptide prevents 7,12-dimethylbenz[alpha]anthracene (DMBA)-induced rat mammary tumorigenesis and investigated the mechanism of action. Dietary administration of soy peptide (3.3 g/rat/day) significantly reduced the incidence of ductal carcinomas (50%), the number of tumors per multiple tumor-bearing rats (49%; P < 0.05), and extended the latency period of tumor development (8.07 +/- 0.92 weeks) compared to control diet animals (10.80 +/- 1.30; P < 0.05). Our results have further demonstrated that soy peptide (1) dramatically inhibits the expression of HSP90, thereby suppressing signaling pathway leading to NF-kappaB activation; (2) induces expression of p21, p53, and caspase-3 proteins; and (3) inhibits expression of VEGF. In agreement with our in vivo data, soy peptide treatment inhibited the growth of human breast MCF-7 tumor cells in a dose-dependent manner and induced apoptosis. Taken together, our in vivo and in vitro results suggest chemopreventive and tumor suppressive functions of isoflavone-deprived soy peptide by inducing growth arrest and apoptosis.
9,10-Dimethyl-1,2-benzanthracene ; Adenocarcinoma/*prevention & control ; Animals ; Apoptosis/*drug effects ; Breast Neoplasms/chemically induced/pathology/*prevention & control ; Cell Line, Tumor ; Chemoprevention ; Female ; Gene Expression Regulation, Neoplastic ; HSP90 Heat-Shock Proteins/genetics/metabolism ; Humans ; Isoflavones/chemistry ; NF-kappa B/genetics/metabolism ; Peptides/chemistry/isolation & purification/therapeutic use ; Rats ; Rats, Sprague-Dawley ; Soybean Proteins/chemistry/*isolation & purification/*therapeutic use ; Soybeans/chemistry

OBJECTIVEThe aim of this study was to explore the effect of celecoxib, a cyclooxygenase-2 inhibitor, on induction of apoptosis and inhibition of angiogenesis in gastric cancer.

METHODSFifty nine gastric cancer patients were randomly divided into 2 groups: celecoxib group (n = 37) and control group (n = 22). The patients in the celecoxib group were treated orally with celecoxib 200 mg twice daily for 7 days before resection. The patients in the control group received surgical resection alone. Another group of 20 healthy subjects were recruited as normal control. The number of apoptotic tumor cells was measured by terminal deoxynucleotidyl transferse-mediated dUTP nick end labeling (TUNEL). The expression of COX-2, VEGF and the microvessel density (MVD) were evaluated by immunohistochemistry.

RESULTSThe TUNEL results showed an increase of apoptosis in the tumor cells after celecoxib treatment in comparison with that in the control group (7.1% +/- 1.0% vs. 6.2% +/- 0.9%, P < 0.05). The expression level of COX-2 and VEGF in the gastric cancer tissues was significantly decreased in the celecoxib group compared with those in the control group (P < 0.05). Furthermore, MVD was also significantly lower in the celecoxib group when compared with that in the control group (30.48 +/- 5.02 vs. 38.98 +/- 4.58, P < 0.05).

CONCLUSIONOral intake of celecoxib can induce apoptosis and suppress angiogenesis in gastric cancer. It may become an effective agent in the treatment of gastric cancer.

Adenocarcinoma ; metabolism ; pathology ; Adult ; Aged ; Apoptosis ; drug effects ; Celecoxib ; Cyclooxygenase 2 ; metabolism ; Cyclooxygenase 2 Inhibitors ; pharmacology ; therapeutic use ; Female ; Humans ; Male ; Microvessels ; pathology ; ultrastructure ; Middle Aged ; Neovascularization, Pathologic ; prevention & control ; Pyrazoles ; pharmacology ; therapeutic use ; Stomach Neoplasms ; metabolism ; pathology ; Sulfonamides ; pharmacology ; therapeutic use ; Vascular Endothelial Growth Factor A ; metabolism

PURPOSE: It is known that cyclooxygenase (COX)-2 expression is increased in Barrett's esophagus and esophageal adenocarcinomas. We studied COX-2 expression and the effect sulindac has on the genesis of Barrett's esophagus and adenocarcinoma in rats undergoing esophagogastroduodenal anastomosis (EGDA). MATERIALS AND METHODS: Fifty-one rats were divided into a control group (n=27), a 500ppm sulindac-treated group (n=15) and 1000 ppm sulindac-treated group (n=9). Randomly selected rats were killed by diethyl ether inhalation at 20 and 40 weeks after surgery. RESULTS: At 40 weeks, rats treated with 1000 ppm sulindac showed narrower esophageal diameter and milder inflammation than the control rats. At 40 weeks, the incidence of Barrett's esophagus was similar between control and sulindac-treated groups, but the incidence of adenocarcinoma was significantly lower in the 1000ppm sulindac-treated group than either the control or 500 ppm sulindac-treated groups. COX-2 was significantly increased in the lower esophagus of control rats killed at 40 weeks. Cyclin D1 expression was negligible in the sulindac- treated group compared with the control group. CONCLUSION: We suggest that the chemopreventive effect of sulindac is related to decreased COX-2 and cyclin D1 expression, which may be influenced by reduced inflammation.
Adenocarcinoma/etiology/metabolism/*prevention & control ; Animals ; Antineoplastic Agents/therapeutic use ; Barrett Esophagus/etiology/metabolism/prevention & control ; Blotting, Western ; Cyclin D1/metabolism ; Cyclooxygenase 2/metabolism ; Duodenogastric Reflux/*complications ; Esophageal Neoplasms/etiology/metabolism/*prevention & control ; Immunohistochemistry ; Male ; Proliferating Cell Nuclear Antigen/metabolism ; Rats ; Rats, Sprague-Dawley ; Sulindac/*therapeutic use