Metformin reduces serum CA199 levels in type 2 diabetes Chinese patients with time-effect and gender difference.

BACKGROUND: This study was designed to clarify the influence of metformin on serum carbohydrate antigen 199 (CA199) levels and its associated factors in Chinese type 2 diabetes mellitus (T2DM) patients. SUBJECTS AND METHODS: In total, 1,253 T2DM patients were enrolled, including a non-metformin group (n = 616), a short-term metformin group (at least 1 week to 2 years; n=325), and a long-term metformin group (≥ 2 years; n = 312). Their clinical and biochemical characteristics were collected and compared. After 1 year, the biochemical parameters were re-examined in 296 patients. Sex hormones were determined, and associations between CA199 and other variables were assessed. RESULTS: At baseline, the incidence of abnormal CA199 levels was 14.7%, 8.9%, and 4.7% in the non-metformin, short-term metformin, and long-term metformin groups, respectively. CA199 levels in females were significantly higher than in males (P < 0.01) and decreased significantly with the time of taking metformin (25.60 ± 13.68 U/mL in non-metformin controls vs. 17.62 ± 10.87 U/mL in the short-term group vs. 10.54 ± 8.14 U/mL in the long-term group; P = 0.000). The correlation and multiple stepwise regression analysis revealed that glycosylated hemoglobin, metformin, gender, total cholesterol, and follicle-stimulating hormone were independent impact factors on CA199 concentrations (all P < 0.05). Binary logistic regression revealed that the risk of abnormal CA199 concentrations of the total population with short-term metformin or long-term metformin treatment decreased 11% (odds ratio = 0.89; P = 0.001) and 30% (odds ratio = 0.70; P = 0.000), respectively, at baseline. After a 1-year follow-up, the incidence of high CA199 level decreased in both the short-term and the long-term metformin group compared with that of controls (P < 0.05). The extent of CA199 decrease in the long-term metformin group was the greatest (-17% vs. -4.9% in the short-term group vs. 3% in controls, P = 0.000), and the group's risk of high blood CA199 level was reduced 67% (odds ratio = 0.33; P = 0.023). The reduction in women was more apparent than that in men (-18% vs. -5%, P = 0.000). CONCLUSIONS: Metformin therapy reduced the CA199 level in Chinese T2DM patients, and its greatest decrease occurred in women with longer therapeutic time.

Chemotherapy-induced transient CEA and CA19-9 surges in patients with metastatic or recurrent gastric cancer.

BACKGROUND: Rising serum tumor markers after chemotherapy are generally considered to indicate tumor progression. However, we have observed a transient increase in carcinoembryonic antigen (CEA) or carbohydrate antigen 19-9 (CA19-9) levels despite clinical benefits from chemotherapy in patients with metastatic or recurrent gastric cancer (MRGC). Therefore, this study was performed to determine the incidence of CEA and CA19-9 surges and their implications on the clinical outcome in MRGC patients. MATERIAL AND METHODS: Fifty-one and 40 patients who had evaluable data for CEA or CA19-9 surges, respectively, were included. Both CEA and CA 19-9 surges were defined as a > 20% increase in these tumor markers from the baseline that was followed by a > 20% drop in subsequent levels compared to the baseline. RESULTS: Of 51 evaluable patients for CEA surges, nine patients (18%) had documented CEA surges. The median time to CEA peak and the duration of the CEA surge were 2.8 (1.7 approximately 7.0) and 9.1 weeks (7.6 approximately 21.0), respectively. Of 40 evaluable patients for CA19-9 surges, seven patients (18%) had CA19-9 surges. The median time to peak and the duration of the CA19-9 surge were 2.3 (1.9 approximately 6.0) and 7.1 weeks (4.3 approximately 16.1), respectively. All patients with CEA or CA19-9 surges had radiographic evidence of benefits from chemotherapy. CONCLUSION: CEA or CA19-9 surges can be observed in MRGC patients receiving chemotherapy. All patients with these surge phenomena had clinical benefits from chemotherapy. An initial rise in CEA or CA19-9 levels after initiation of chemotherapy should not be used as an indicator of progressive disease.

Pharmacodynamic and pharmacokinetic study of oral Curcuma extract in patients with colorectal cancer.

Curcuma spp. extracts, particularly the dietary polyphenol curcumin, prevent colon cancer in rodents. In view of the sparse information on the pharmacodynamics and pharmacokinetics of curcumin in humans, a dose-escalation pilot study of a novel standardized Curcuma extract in proprietary capsule form was performed at doses between 440 and 2200 mg/day, containing 36-180 mg of curcumin. Fifteen patients with advanced colorectal cancer refractory to standard chemotherapies received Curcuma extract daily for up to 4 months. Activity of glutathione S-transferase and levels of a DNA adduct (M(1)G) formed by malondialdehyde, a product of lipid peroxidation and prostaglandin biosynthesis, were measured in patients' blood cells. Oral Curcuma extract was well tolerated, and dose-limiting toxicity was not observed. Neither curcumin nor its metabolites were detected in blood or urine, but curcumin was recovered from feces. Curcumin sulfate was identified in the feces of one patient. Ingestion of 440 mg of Curcuma extract for 29 days was accompanied by a 59% decrease in lymphocytic glutathione S-transferase activity. At higher dose levels, this effect was not observed. Leukocytic M(1)G levels were constant within each patient and unaffected by treatment. Radiologically stable disease was demonstrated in five patients for 2-4 months of treatment. The results suggest that (a) Curcuma extract can be administered safely to patients at doses of up to 2.2 g daily, equivalent to 180 mg of curcumin; (b) curcumin has low oral bioavailability in humans and may undergo intestinal metabolism; and (c) larger clinical trials of Curcuma extract are merited.

[Changes in the levels of tumor markers in those working with different chemically active substances]. / Izmenenie urovnei opukholevykh markerov u rabotaiushchikh s razlichnymi khimicheski aktivnymi veshchestvami.

Groups at risk for malignant neoplasia were identified among workmen occupationally exposed to different chemical substances, using immunoradiometric and enzyme immunoassays of tumor-associated antigens. Exposure to the above occupational hazard was found to affect the workmen and cause certain chronic illness accompanied by some increase in concentration of a number of tumoral markers. Increase in tumour antigens suggests indirectly that the chemical substances may have carcinogenic activity. We have every reason to recommend these tests as an additional method for identification of groups at high risk for subsequent development of tumours in the digestive system and reproductive organs of persons occupationally exposed to chemical substances.