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Age distribution of cancer in mice: the incidence turnover at old age.

We have studied cancer incidence in mice as a function of age in those cohorts where the rodents are allowed to live very close to their full natural lifetime. We find that the incidence rises as a function of age, but then flattens and turns over at an age of about 800 days. This behaviour is similar to that which we observed (Pompei and Wilson, 2001) in the Surveillance, Epidemiology, and End Results (SEER) data where the age distribution of human cancer incidence turns over at about age 80. Although other fits are possible, the three-parameter beta function model fits both the mouse data and the human data well. The beta model implies, and the data do not deny, the interpretation that cancer is not a certainty and mice may also outlive their cancers, although high-dose cohort results suggest cancer might be certain if dose is sufficiently high. Limited data suggest that the cancer age distribution, including the turnover, may be time shifted by dietary restriction.

Age Distribution↗

Prognostic model for predicting survival in men with hormone-refractory metastatic prostate cancer.

PURPOSE: To develop and validate a model that can be used to predict the overall survival probability among metastatic hormone-refractory prostate cancer patients (HRPC). PATIENTS AND METHODS: Data from six Cancer and Leukemia Group B protocols that enrolled 1,101 patients with metastatic hormone-refractory adenocarcinoma of the prostate during the study period from 1991 to 2001 were pooled. The proportional hazards model was used to develop a multivariable model on the basis of pretreatment factors and to construct a prognostic model. The area under the receiver operating characteristic curve (ROC) was calculated as a measure of predictive discrimination. Calibration of the model predictions was assessed by comparing the predicted probability with the actual survival probability. An independent data set was used to validate the fitted model. RESULTS: The final model included the following factors: lactate dehydrogenase, prostate-specific antigen, alkaline phosphatase, Gleason sum, Eastern Cooperative Oncology Group performance status, hemoglobin, and the presence of visceral disease. The area under the ROC curve was 0.68. Patients were classified into one of four risk groups. We observed a good agreement between the observed and predicted survival probabilities for the four risk groups. The observed median survival durations were 7.5 (95% confidence interval [CI], 6.2 to 10.9), 13.4 (95% CI, 9.7 to 26.3), 18.9 (95% CI, 16.2 to 26.3), and 27.2 (95% CI, 21.9 to 42.8) months for the first, second, third, and fourth risk groups, respectively. The corresponding median predicted survival times were 8.8, 13.4, 17.4, and 22.80 for the four risk groups. CONCLUSION: This model could be used to predict individual survival probabilities and to stratify metastatic HRPC patients in randomized phase III trials.

Adenocarcinoma↗

[A clinicopathologic and immunohistochemical study on 76 cases of gastrointestinal stromal tumors].

OBJECTIVE: To study the morphologic and immunohistochemical features of gastrointestinal stromal tumors (GISTs) and to explore the reference parameters for malignancy. METHODS: Seventy six (76) cases of primary GISTs were distinguished from a group of gastrointestinal mesenchymal tumors by use of a panel of antibodies such as CD117, CD34 by immunohistochemical EnVision method, their biologic behaviors were analyzed by including their follow-up data. RESULTS: All patients were adults, age range 32 to 81 years (mean 54 year), male 39 cases and female 37 cases; the tumors were situated in stomach (36 cases), in small intestine (23 cases), colon (2 cases) and rectum (15 cases). The most common symptoms were abdomen mass, vague pain and GI bleeding. Forty eight (48) cases were mainly located within the muscularis propria, 25 cases outside the serosa, and 3 cases below the mucosa. Grossly, they were of soft consistency often with hemorrhage, cystification or necrosis. Microscopically, the tumors were composed of spindle cells (46 cases) or epithelioid cells (9 cases) and of both cells (21 cases), arranged in interlacing fasicles, diffusing sheets, pallisading, whirling, alveolar and giant pseudo-rosette shapes. Tumor cells often had abundant cytoplasm with light to moderate eosinophilic or slight basophilic in staining, the nuclei generally showed spindle, blunted ends, round or signet in shape with nucleoli. Immunohistochemically, CD117 and CD34 showed diffuse strong expression, the positive rates were 98.7% and 68.4% respectively, alpha-SMA, MSA, S-100, PGP9.5 showed focal expression, the positive rates were 25.0%, 19.7%, 23.7% and 17.1% respectively, vimentin were all positive and desmin, GFAP, NF were all negative. Nine cases were benign, 19 cases borderline and 48 cases malignant. Follow-up of 20 cases with benign and borderline tumors found patients alive without tumor. In the malignant group of 34 cases, 10 cases were alive without tumor, 10 cases developed recurrence or metastasis, and 14 cases died of tumor. Coagulative necrosis, mitotic activity over 10/50HPF, high cellularity and obvious pleomorphism were all in the malignant group. In this group, tumor necrosis, adhesion in operation, tumor, over 5 cm in diameter, mitotic activity over 5/50HPF had significant differences among three groups and the 3 years survival rate had a significant difference in tumors with or without coagulative necrosis and also in tumors with or without mitotic activity over 5/50HPF. CONCLUSIONS: GISTs predominantly occurred in middle aged or old patients, the tumors had varied cell types and different arrangements, the immunohistochemical characters were positive for CD117 and CD34, negative for desmin, occasional positive for alpha-SMA, MSA, S-100 and PGP9.5, which were helpful to differentiate GIST from leiomyomas and Schwannomas. Coagulative necrosis, mitotic activity over 10/50HPF, high cellularity with obvious pleomorphism were also helpful parameters for diagnosis of malignancy aside from metastasis and invasion. Adhesion, over 5 cm in diameter and mitotic activity over 5/50HPF but less than 10/50HPF might be the potential malignant parameters.

Adult↗

Reduction of 1-methyl-1-nitrosourea-induced mammary gland carcinoma by in vivo application of immunostimulatory CpG motifs in Sprague-Dawley rats.

In the present work the role of 13-cis retinoic acid and CpG oligodeoxynucleotides (CpG-ODN) in a 1-methyl-1-nitrosourea (MNU)-induced mammary gland carcinoma animal model was investigated. Treatment with both components, applied either alone or in combination, induced a significant decrease of the tumour burden and the volume of tumours only in rats that received CpG-ODN (p = 0.046, compared to the MNU control group). The data indicate that the Th-1 biased immunostimulatory capacities of CpG motifs may play a significant role in induction of protective immune responses against mammary gland tumours in Sprague-Dawley rats.

Alkylating Agents↗

Serum copper levels in carcinoma of ovary and cervix.

The role of serum copper level (SCL) as a diagnostic and prognostic tool in genital tract malignancies was evaluated. SCL was employed as a marker for response to treatment (surgical/radiotherapy). 129 women attending gynaecology outpatient department or admitted in the gynecology ward were studied. Of these 77 patients in the disease (study) group were proven cases of genital tract malignancies and 52 served as controls. Outcome measures studied were: SCL levels estimated before initiation of any treatment i.e. surgery/radiotherapy; thereafter, at two weeks after completion of treatment. Follow up of the study subjects was done between 4-8 weeks and 8-10 weeks, when the patients were evaluated for any recurrence of disease and SCLs were also estimated. Kruskal-Wallis one-way analysis of variance determined whether values varied significantly among the different groups studied. Mean SCLs were found to be significantly elevated in cases of Ca ovary (n = 15), early CaCx (n = 14) and late CaCx (n = 48), as compared to the control group, comprising of women with no signs and symptoms of malignancy (n = 52). SCLs decreases significantly (P < 0.001) after treatment of Ca ovary and CaCx. These results indicate a possible clinical usefulness of estimating serum copper levels in women with genital tract cancer and suggest a role for SCL in the evaluation of the disease activity and as a prognostic tool in the management of genital malignancies.

Adolescent↗

Induced liver tumour further support to a genetic marker with its high correlation with chorioallantoic membrane phenotypes in selected layer lines.

The conventional chorioallantoic membrane (CAM) phenotype assay was conducted using 11-day-old embryonatic eggs of white Leghorn strains, each inoculated with 0.2 ml of subgroup A Rous sarcoma virus (RSV) and subgroup C RSV separately containing 10(3)pfu ml(-1). Eggs were further incubated for hatching. Harvesting of CAMs for counting of pocks and monitoring chicks for liver tumour (LT) mortality during 4 weeks of post-hatching period were followed. The conversely associated phenotype (CAP) incidence i.e. CAM(+) LT(-) and CAM(-) LT(+) was observed in all three lines for both subgroup A and C virus infection. The LT deaths of chicks in all strains occurred within 21 days post-hatch irrespective of virus subgroups. The regression analysis of %LT death (transformed data) distributed within pock count range (PCR) basis was performed. The regression coefficients (b(i)'s) were found to be non-significant, indicating that %LT death did not correlate with number of particles that entered the cells because the chicks that had at least 25 pock counts in CAMs died with few exceptions. This study upheld the view that the CAM phenotypes (S and R) under the control of a pair of alleles, a(s) and a(r) at the tva locus and c(s) and c(r) at the tvc locus as reported extensively. Because of a high correlation coefficients between CAM and LT phenotypes [S and LT(+)] in respect of subgroup A (r = 0.72) and subgroup C (r = 0.81) infection, it is obvious that one could postulate a pleiotropic control of the two traits by the tva and tvc genes, respectively. Indeed fitting a 4-allele model in both tva and tvc locus, suggesting that CAPs are the indicator for nullifying the conventional 2-allele model proposed for the induced tumour expression phenotypes by leukosis sarcoma viruses.

Alleles↗

Parametric mixture model for analysing relative survival of patients with multiple cancers.

BACKGROUND: This study aimed to provide a parametric mixture model for analysing relative survival and cure rates of patients with multiple cancers. METHODS: A new model was introduced by extending a parametric mixture model on relative survival of patients with a single cancer. The model was applied to empirical data on lung cancer as a first and second tumour after a first localised colorectal cancer. RESULTS: Survival and cure from subsequent cancer are estimatable with the parametric mixture model on relative survival of patients with multiple cancers. Survival from lung cancer does not differ between the first and second tumour, but there is suggestive evidence that survival from second lung cancer is higher than that from the first lung cancer. DISCUSSION: Relative survival analysis of patients with multiple cancers can be extended to incorporate cure rates and excess hazards related to the individual cancers. Prognostic factors can be included in the model.

Adult↗