Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0699790 (colon cancer)
 28,837 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Monocyte derived macrophages from breast and gynecologic cancer patients generally do not acquire enhanced cytotoxicity for human tumor cells after incubation with bacterial lipopolysaccharide (LPS) whereas the macrophages isolated from colon and hematologic cancer patients are cytotoxic. However, it was also found that 75% of the patients possessing cytotoxic macrophages also had a plasma factor which suppressed macrophage mediated cytotoxicity. The plasma inhibitory factor obtained from a colon cancer patient was purified utilizing Sephadex G-200 column chromatography and 4 fractions (A, B, C and D) with inhibitory activity, were isolated. When a plasma sample obtained from a colon cancer patient found to be lacking the inhibitor of macrophage cytotoxicity was fractionated, 2 fractions were isolated with inhibitory activity. These fractions corresponded to fractions A and C of the inhibitory sample. Pooled AB+ serum was also fractionated and no inhibitory fractions could be isolated. The inhibitory factors were further characterized and it was found that fractions A and B appear to be inhibitors of lysosomal enzyme activity and fraction C appears to be an inhibitor of protease activity. When the plasma from cancer patients known to possess an inhibitor of macrophage mediated cytotoxicity was examined for the presence of fraction A, B, C and D, it was found that every colon cancer patient studied possessed inhibitors A, B, C and D. Breast cancer patients possessed some combination of A, B and C but all lacked fraction D and the gynecologic cancer patients possessed some combination of factors A, B and D but they all lacked inhibitor C.
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PMID:Cytotoxicity of cancer patients' macrophages for tumor cells: purification and characterization of plasma inhibitory factors obtained from colon cancer patients. 634 Dec 66

The clinical importance of atypical glandular cells of undetermined significance (AGUS) on cervicovaginal smear has not been well defined. Between January 1990 and April 1996, 127 smears were reported as showing AGUS changes by the cytopathology division at the University of Massachusetts Medical Center. The medical records of these women were reviewed: 17 women were excluded because of previous hysterectomy or gynecologic cancer, 85 were biopsied, 16 were followed by repeat smears, and 9 were lost to follow-up. Forty-four women had negative biopsies or cervicitis. There were 15 endometrial lesions: 10 hyperplasias (2 with atypia) and 5 adenocarcinomas. Twenty-five women had cervix lesions including 3 endocervical atypias, 12 low-grade cervical intraepithelial neoplasia (CIN), 6 high-grade CIN, one adenocarcinoma in situ, and 3 invasive adenocarcinomas. One patient had ovarian cancer. Two of the 16 women followed by repeat pap smear eventually had a cancer diagnosis: one with cervix cancer and one with colon cancer. We were unable to identify a subgroup of women with AGUS who were at increased risk for serious pathology when we compared multiple demographic variables, symptoms, or the presence of coexistent squamous abnormalities on cervical cytology. The mean age of the 15 women with endometrial lesions was 59.9 years, which was significantly older than those patients with cervix lesions who had a mean age of 38.9 years. The presence of AGUS on cervical cytology is a marker for significant gynecologic neoplasia and should be investigated with colposcopically directed biopsies, endocervical curettage, and, in older women, endometrial biopsy.
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PMID:Neoplasia associated with atypical glandular cells of undetermined significance on cervical cytology. 915 44

The effect of the addition of G-CSF to carboplatin, ifosfamide and doxorubicin (CIA) at the maximally tolerated dose (MTD) was studied in a phase I clinical trial. Nine patients with incurable solid tumors were treated: six endometrial and epithelial ovarian cancers, one colon cancer with pelvic masses and two unknown primary cancers. The carboplatin dose was calculated using the Calvert formula and administered in a standard 30-min intravenous infusion. The initial carboplatin dose was AUC 4.0 mg/ml per min. Fixed doses of ifosfamide (1.25 g/m2 per day), mesna (1.0 g/m2 per day, and doxorubicin (15 mg/m2 per day) were combined and given as a 4-day continuous intravenous infusion in an attempt to decrease nonhematologic toxicity. The dose-limiting toxicity of CIA was myelosuppression, mainly neutropenia and thrombocytopenia. Nonhematologic toxicities were hemorrhagic cystitis, weakness, fatigue, and nausea and vomiting. The MTD for CIA was established at the first dose level of carboplatin (4.0 mg/ml per min). Following this, G-CSF was added to the regimen in an unsuccessful effort to escalate the carboplatin dose. Free and total carboplatin pharmacokinetics were determined using flameless atomic absorption spectroscopy. There was one complete response and one partial response among eight evaluable patients. Both responding patients had advanced ovarian cancer. We conclude that carboplatin dose intensification beyond an AUC of 4.0 mg/ml per min is not made feasible by the addition of G-CSF to infusional doxorubicin and ifosfamide in patients with advanced gynecologic cancer.
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PMID:A phase I trial of AUC-directed carboplatin with infusional doxorubicin and ifosfamide plus G-CSF in patients with advanced gynecologic malignancies. 1112 46

Retinoids are natural and synthetic derivatives of vitamin A that have great promise for cancer therapy and chemoprevention. Of the retinoids developed so far, 4-(N-hydroxyphenyl)retinamide (4-HPR or fenretinide) appears to have the best therapeutic potential in vitro and in vivo and is currently being tested in clinical trials for cancer prevention and therapy. To develop other potentially potent antitumor agents, we synthesized 85 retinoid derivatives. In an initial screening of these synthetic retinoids using the HCT116 colon cancer cell line, we found that 4-amino-2-(butyrylamino)phenyl(2E,4E,6E,8E)-3,7-dimethyl-9-(2,6,6-trimethyl-1-cyclohexenyl)-2,4,6,8-nonatetraenoate (ABPN or CBG41) induced the greatest growth inhibition, with an IC(50) value of 0.6 microM. Subsequent studies in other cancer cell lines indicated that ABPN was much more growth-inhibitory than all-trans retinoic acid or 4-HPR. Compared to 4-HPR, ABPN induced 5.5- to 70.0-fold more growth inhibition in most cancer cells, with the exception of gynecologic cancer cells. In these cells, the antiproliferative effect was only 1.5- to 2.8-fold more than 4-HPR. We examined the molecular mechanism underlying the difference in growth inhibition between 4-HPR and ABPN. DAPI staining, DNA fragmentation, FACS and Western blotting analyses suggest that ABPN induced apoptosis by activating caspase-3 and -8, which may result in increased PARP cleavage. Unlike 4-HPR, ABPN activated all 3 RAR isotypes to an extent similar to AtRA. In addition, ABPN significantly inhibited AP-1 transcriptional activity and thus greatly suppressed the expression of the matrix metalloproteinase -1, -2 and -3 genes, which are involved in tumor invasion. These results suggest that ABPN may be a promising retinoid derivative offering not only enhanced cytotoxicity, but also increased inhibition of tumor invasiveness.
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PMID:Novel retinoic acid derivative ABPN has potent inhibitory activity on cell growth and apoptosis in cancer cells. 1460 Oct 67

Ovarian cancer is the second most common type of female reproductive cancer, and more women die from ovarian cancer than from cervical cancer and uterine cancer combined. Currently, there is no strategy for early detection of ovarian cancer that reduces ovarian cancer mortality. Taking a detailed personal and family history for breast, gynecologic, and colon cancer facilitates categorizing women based on their risk (average risk or high risk) of developing epithelial ovarian cancer. Women with a strong family history of ovarian, breast, or colon cancer may have hereditary breast and ovarian cancer syndrome (BRCA mutation) or hereditary nonpolyposis colorectal cancer (Lynch syndrome), and these women are at increased risk of developing ovarian cancer. Women with these conditions should be referred for formal genetic counseling to better assess their cancer risk, including their risk of ovarian cancer. If appropriate, these women may be offered additional testing for early detection of ovarian cancer. The use of transvaginal ultrasonography and tumor markers (such as cancer antigen 125), alone or in combination, for the early detection of ovarian cancer in average-risk women have not been proved to reduce mortality, and harms exist from invasive diagnostic testing (eg, surgery) resulting from false-positive test results. The patient and her obstetrician-gynecologist should maintain an appropriate level of suspicion when potentially relevant signs and symptoms of ovarian cancer are present.
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PMID:Committee Opinion No. 716 Summary: The Role of the Obstetrician-Gynecologist in the Early Detection of Epithelial Ovarian Cancer in Women at Average Risk. 2883 78

Ovarian cancer is the second most common type of female reproductive cancer, and more women die from ovarian cancer than from cervical cancer and uterine cancer combined. Currently, there is no strategy for early detection of ovarian cancer that reduces ovarian cancer mortality. Taking a detailed personal and family history for breast, gynecologic, and colon cancer facilitates categorizing women based on their risk (average risk or high risk) of developing epithelial ovarian cancer. Women with a strong family history of ovarian, breast, or colon cancer may have hereditary breast and ovarian cancer syndrome (BRCA mutation) or hereditary nonpolyposis colorectal cancer (Lynch syndrome), and these women are at increased risk of developing ovarian cancer. Women with these conditions should be referred for formal genetic counseling to better assess their cancer risk, including their risk of ovarian cancer. If appropriate, these women may be offered additional testing for early detection of ovarian cancer. The use of transvaginal ultrasonography and tumor markers (such as cancer antigen 125), alone or in combination, for the early detection of ovarian cancer in average-risk women have not been proved to reduce mortality, and harms exist from invasive diagnostic testing (eg, surgery) resulting from false-positive test results. The patient and her obstetrician-gynecologist should maintain an appropriate level of suspicion when potentially relevant signs and symptoms of ovarian cancer are present.
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PMID:Committee Opinion No. 716: The Role of the Obstetrician-Gynecologist in the Early Detection of Epithelial Ovarian Cancer in Women at Average Risk. 2883 87

Ovarian cancer is the most deadly gynecologic cancer among women worldwide. Poor response to current treatment makes it necessary to discover new diagnostic biomarkers to detect the cancer early and develop new and effective prevention strategies. Calcitriol, the active metabolite of vitamin D, protects against multiple cancers through unelucidated mechanisms. The oncogenic long non-coding RNA (lncRNA) CCAT2 (colon cancer associated transcript 2) is overexpressed in ovarian cancer. Here, we foundd that calcitriol inhibited CCAT2 expression in ovarian cancer cell lines. Treatment with calcitriol inhibited ovarian cancer cell proliferation, migration, and invasion. As a result of CCAT2 inhibition, calcitriol decreased the binding of transcription factor TCF7L2 (TCF4) to the MYC promoter, resulting in the repression of c-Myc protein expression. Our results suggest a novel anti-cancer mechanism of vitamin D by targeting CCAT2 in ovarian cancer. The findings may help develop vitamin D as a practical and inexpensive nutraceutical for ovarian cancer prevention.
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PMID:Vitamin D Suppresses Ovarian Cancer Growth and Invasion by Targeting Long Non-Coding RNA CCAT2. 3223 Sep 36