These results show that peripherally circulating tumor cells are influenced by systemic chemotherapy and that an increase (even after initial response to therapy) of 10-fold or more at the end of therapy is a strong predictor of relapse and a surrogate marker for the aggressiveness of the tumor cells.

Nonmass lesions were the major cause of false-positive breast MRI findings. BI-RADS descriptors are not sufficient for differentiating benign and malignant nonmass lesions.

Based on the high incidence of loss of heterozygosity for loci on chromosome 17p in the vicinity of the p53 locus in human breast tumors, we investigated the frequency and effects of mutations in the p53 tumor suppressor gene in mammary neoplasia. We examined the p53 gene in 20 breast cancer cell lines and 59 primary breast tumors. Northern blot analysis, immunoprecipitation, and nucleotide sequencing analysis revealed aberrant mRNA expression, overexpression of protein, and point mutations in the p53 gene in 50% of the cell lines tested. A multiplex PCR assay was developed to search for deletions in the p53 genomic locus.

Purpose: To determine the safety, gene transfer, host immune response, and pharmacokinetics of a replication -deficient adenovirus encoding human, recombinant, wild -type p53 ( SCH 58500 ) delivered into the peritoneal cavity ( i.p. ) alone and sequentially in combination with platinum -based chemotherapy, of patients with recurrent ovarian, primary peritoneal, or fallopian tube cancer containing aberrant or mutant p53. Methods: SCH 58500 was administered i.p. to three groups of patients with heavily pretreated recurrent disease. Group 1 ( n = 17 ) received a single dose of SCH 58500 escalated from 7.5Â10 10 to 7.5Â10 12 particles. Group 2 ( n = 9 ) received two or three doses of SCH 58500 given alone for one cycle, and then with chemotherapy for two cycles. The SCH 58500 dose was further escalated to 2.5Â10 13 particles / dose in group 2. A third group ( n = 15 ) received a 5 -day regimen of SCH 58500 given at 7.5Â10 13 particles / dose per day i.p. alone for cycle 1 and then with intravenous carboplatin / paclitaxel chemotherapy for cycles 2 and 3. Results: No dose -limiting toxicity resulted from the delivery of 236 / 287 ( 82.2% ) planned doses of SCH 58500. Fever, hypotension abdominal complaints, nausea, and vomiting were the most common adverse events. Vectorspecific transgene expression in tumor was documented by RT -PCR in cells from both ascitic fluid and tissue biopsies. Despite marked increases in serum adenoviral antibody titers, transgene expression was measurable in 17 of 20 samples obtained after two or three cycles of SCH 58500. Vector was detectable in peritoneal fluid by 24 hours and persisted for as long as 7 days whereas none was detected in urine or stool. There was poor correlation between CT scans and CA125 responses. CA125 responses, defined as a greater than 50% decrement in serum CA125 from baseline, were documented in 8 of 16 women who completed three cycles of the multidose regimen. Conclusion: CT scans are not a valid measure of response to i.p. SCH 58500 due to extensive adenoviral -induced inflammatory changes. Intraperitoneal SCH 58500 is safe, well tolerated, and combined with platinum -based chemotherapy can be associated with a significant reduction of serum CA125 in heavily pretreated patients with recurrent ovarian, primary peritoneal, or fallopian tube cancer.

Background: In vitro and observational epidemiological studies suggest that vitamin D may play a role in cancer prevention. However, the relationship between vitamin D and ovarian cancer is uncertain, with observational studies generating conflicting findings. A potential limitation of observational studies is inadequate control of confounding. To overcome this problem, we used Mendelian randomization (MR) to evaluate the association between single nucleotide polymorphisms (SNPs) associated with circulating 25-hydroxyvitamin D [25(OH)D] concentration and risk of ovarian cancer. Methods: We employed SNPs with well-established associations with 25(OH)D concentration as instrumental variables for MR: rs7944926 (DHCR7), rs12794714 (CYP2R1) and rs2282679 (GC). We included 31 719 women of European ancestry (10 065 cases, 21 654 controls) from the Ovarian Cancer Association Consortium, who were genotyped using customized Illumina Infinium iSelect (iCOGS) arrays. A two-sample (summary data) MR approach was used and analyses were performed separately for all ovarian cancer (10 065 cases) and for high-grade serous ovarian cancer (4121 cases). Results: The odds ratio for epithelial ovarian cancer risk (10 065 cases) estimated by combining the individual SNP associations using inverse variance weighting was 1.27 (95% confidence interval: 1.06 to 1.51) per 20 nmol/L decrease in 25(OH)D concentration. The estimated odds ratio for high-grade serous epithelial ovarian cancer (4121 cases) was 1.54 (1.19, 2.01). Conclusions: Genetically lowered 25-hydroxyvitamin D concentrations were associated with higher ovarian cancer susceptibility in Europeans. These findings suggest that increasing plasma vitamin D levels may reduce risk of ovarian cancer.