Biomedical subjects

M Tan

Publications and source records attributed to M Tan.

At least 109 records · Page 6Linked to original sources

PubMed1998

[Clinical evaluation of cardiac troponin I in ischemic heart diseases].

The detection of cardiac troponin I(cTnI), including serum or plasma, was evaluated in 114 patients with ischemic heart diseases or other heart diseases. The results were that the sensitivity of cTnI detection(qualitative analysis, cutoff is 0.2 ng.ml-1) was higher than that of creatine kinase(CK), creatine kinase-MB(CK-MB), alpha-hydroxybutyrate dehydrogenase(alpha-HBD), lactic dehydrogenase(LDH), and aspartic transaminase(AST) for diagnosing acute myocardial infarction (AMI) (93.2% vs 68.2%, 68.2%, 65.9%, 65.9%, and 75.0%; P < 0.05; respectively). The specificity of cTnI detection was higher than that of alpha-HBD, LDH, and AST(95.2% vs 81.0%, 73.8%, and 54.0%; P < 0.05; respectively) and similar to CK and CK-MB(95.2% vs 83.3% and 83.3%; P > 0.05; respectively). On the other hand, the sensitivity of cTnI in patients with unstable angina pectoris was 45.5%. It was higher than stable angina pectoris and lower than AMI. The results suggest that the cardiac troponin I is a better cardiac injury marker than other cardiac markers for diagnosing AMI.

Adult↗

PubMed1998

[Analysis for the auditory brainstem responses of human with wavelet transform].

To find out the value of wavelet transform when it is applied in analysis of human's auditory brainstem responses (ABR). The subjects was divided into two groups, one group is normal hearing subjects (14 cases, 28 ears) and another is sensorial hearing loss subjects (17 cases, 27 ears). ABR of the two groups was collected and represented with wavelet transform respectively. The signals of pre- and post being transferred was contrasted and dealt with statistics. Similar to the analysis of guinea pig's ABR, the wavelet transform scale 3 is mostly adequate to the analysis of human's ABR. The time's field after transforming is not changed and the emerged rate of wave I is increased, IV-V compound is divided clearly. So the measurement of I-V range is more precise. Analysing human's ABR with wavelet transform is more precise in measurement of I-V range than with former methods.

Adult↗

PubMed1998

Infrequent mutation of the p16/MTS1 gene and overexpression of cyclin-dependent kinase 4 in human primary soft-tissue sarcoma.

The pl6INK4a/MTS1 (p16) gene encodes a specific inhibitor of cyclin-dependent kinase (CDK)4 and CDK6. The p16 gene is frequently mutated or deleted in many types of cancer cell lines as well as in certain types of primary tumors. p16 knockout mice are viable but predisposed to sarcoma and B-cell lymphoma. To investigate the role of p16 in human soft-tissue sarcoma tumor progression, we examined the p16 gene by Southern blot analysis and PCR sequencing in 30 pairs of primary soft-tissue sarcomas and autologous normal tissue. Only one tumor sample showed possible rearrangement of the p16 gene. In contrast, Western blot analysis of the p16 protein in 20 pairs of samples showed decreased p16 expression in only 20% of the tumors but elevated p16 expression in 40% of the tumors when compared with the autologous normal controls. Overexpression of p16 was not concomitant with loss of the RB protein as is found in several other types of cancers, because more than one-half of the tumors with increased p16 expression also had high levels of RB protein. On the other hand, the p16 target protein CDK4 was overexpressed in at least 60% of the tumors. In the majority of cases, CDK4 overexpression accompanied elevated p16 and/or RB levels. Our results suggest that: (a) alteration of the p16 gene is infrequent in primary soft-tissue sarcoma; (b) Cdk4 may act as an oncogene in soft-tissue sarcoma; and (c) elevated p16 and RB levels might be the result of compensatory up-regulation of these proteins to counteract CDK4 overexpression in these tumors. Our results also suggest that it is more informative to examine aberrations in the "p16-CDK4/cyclin D-RB" pathway than to selectively examine individual components in this pathway when investigating genetic changes involved in human malignancy.

Animals↗

PubMed1998

Clinical trial designs based on sequential conditional probability ratio tests and reverse stochastic curtailing.

We propose a group sequential method based on the sequential conditional probability ratio test and show that it has the conservatism desired in practice. We also propose calculating the discordant probability, that is, the probability that the sequential test concludes differently from a fixed-sample test at the planned end of the trial, recognizing that this probability could be substantial, even if the sequential test has the same size and power as the fixed-sample size test at the planned end of the study. In addition, we show that the proposed method can be used as a stochastic curtailing tool. Thus, the method accommodates unplanned interim analyses as well as those deemed necessary based on data trends, virtually without inflating the type I error, but it is less conservative than the usual stochastic curtailing. The method is implemented through an interactive computer program.

Adrenergic beta-Antagonists↗

PubMed1998

Wild-type p53 and a p53 temperature-sensitive mutant suppress human soft tissue sarcoma by enhancing cell cycle control.

Soft-tissue sarcomas are a heterogeneous group of tumors that are putatively mesenchymal in origin. Therapeutic advances in this disease have been limited over the past several decades. Approximately one-half of all patients will ultimately succumb, usually to uncontrollable pulmonary metastases. Although little is known about the underlying molecular determinants driving soft-tissue sarcoma inception, proliferation, and metastasis, mutation of the p53 gene is the most frequently detected molecular alteration in this disease. Accordingly, we were interested in determining whether transduction of wild-type (wt) p53 into soft-tissue sarcomas bearing mutated p53 genes might alter the malignant phenotype. SKLMS-1 is a human-derived leiomyosarcoma cell line with a codon 245 p53 point mutation. Cationic liposome was used to transfect wt p53 or 143Ala temperature-sensitive mutant p53 into this cell line. SKLMS-1 stable transfectants expressing wt p53 had decreased cell proliferation in vitro, decreased in vitro colony formation in soft agar, and decreased tumorigenicity in severe combined immunodeficient mice in vivo. Flow cytometric analysis of cell cycle components demonstrated markedly increased G1 cell cycle arrest and decreased entry into S phase, which corresponded to the induction of p21cip1 protein in the transfectants. Using SKLMS-1 stable transfectants expressing the 143Ala p53 temperature-sensitive mutant, we demonstrated the kinetics of and the causal relationship between wt p53 expression, the wt p53-dependent induction of cell cycle inhibitor p21cip1, and inhibition of cell cycle progression in p53-transfected SKLMS-1 cells. The ability to restore wt p53 growth-regulatory functions in soft-tissue sarcoma may ultimately be useful as a future therapy in patients with soft-tissue sarcomas.

Animals↗

PubMed1997

Systemic chemotherapy for gastric carcinoma followed by postoperative intraperitoneal therapy: a final report.

BACKGROUND: Because only approximately 50% of gastric carcinomas are resectable for cure, the authors hypothesized that effective systemic preoperative (neoadjuvant) chemotherapy, aimed at decreasing the size and extent of the primary tumor and eradicating distant microscopic disease, may increase the rate of resectability and have a greater impact on survival than postoperative (adjuvant) treatment alone. In addition, because the peritoneal cavity is the most common site of first recurrence after successful gastric cancer resection, intraperitoneal (IP) chemotherapy seemed a logical choice for postoperative (adjuvant) treatment. METHODS: Fifty-nine patients with invasive primary gastric adenocarcinoma who were deemed resectable for cure entered a clinical trial that called for 2 cycles of protracted infusion 5-fluorouracil with weekly leucovorin and cisplatin chemotherapy followed by surgery. Approximately 3-4 weeks after potentially curative surgery, patients were scheduled to receive two cycles of IP 5-fluoro-2'deoxyuridine and cisplatin. RESULTS: Of the 59 patients studied, 58 (98%) received both cycles of systemic chemotherapy. Fifty-six patients (95%) underwent surgery: 40 patients (71%) had resections intended to cure for Stage 0-IIIB disease, 15 patients (27%) had palliative surgery for Stage IV gastric carcinoma, and one patient died intraoperatively without being staged. Two patients refused surgery, and the remaining patient died of progressive disease prior to surgery. Thirty-one of the 40 patients who underwent curative surgery completed both cycles of postoperative IP therapy; 4 patients received only 1 cycle. Three patients (5%) died secondary to treatment complications. There were two operative deaths, and one patient died of peritonitis associated with Grade 4 granulocytopenia. Nine of the 40 patients (23%) whose carcinomas were resected for cure had recurrent carcinoma. With a median follow-up period now exceeding 45 months, the calculated median survival for the 59 patients entered into the trial is >4 years. CONCLUSIONS: This program of preoperative systemic and postoperative IP chemotherapy has been found to be safe and appears to decrease gastric carcinoma recurrence rates and increase survival compared with historic controls.

Adenocarcinoma↗

PubMed1997

Overexpression of the c-erbB-2 gene enhanced intrinsic metastasis potential in human breast cancer cells without increasing their transformation abilities.

Overexpression of the c-erbB-2 gene-encoded p185 has been reported in approximately 30% of human breast cancers and has been correlated with lymph node metastasis and poor prognosis in breast cancer patients. To investigate whether overexpression of p185 can enhance the metastatic potential of human breast cancer cells, we have introduced the human c-erbB-2 gene into the very low p185-expressing MDA-MB-435 human breast cancer cells and established 435.eB transfectants that express higher levels of p185. In this study, we compared the metastatic phenotypes of the parental MDA-MB-435 cells and the 435.eB transfectants. In vivo experimental metastasis assays in which we injected MDA-MB-435 parental cells or 435.eB transfectants into the tail veins of ICR-SCID mice demonstrated that mice injected with p185-overexpressing 435.eB transfectants formed significantly more metastatic tumors than the mice injected with parental and control cells. The changes in experimental metastatic potential in vivo were accompanied by increased invasiveness in vitro. In addition, the secretion of basement membrane-degradative enzymes, which is an important step in the invasion and metastasis process, was also increased in the p185-overexpressing 435.eB transfectants. These results indicated that p185 overexpression can enhance the metastatic potential of MDA-MB-435 human breast cancer cells. To investigate whether enhanced metastatic potential in the p185-overexpressing 435.eB transfectants was the result of increased cancer cell growth and transformation potential, we compared the growth rate, anchorage-independent growth ability, and tumorigenicity of the 435.eB transfectants with that of the parental cells. The transfectants and the parental cells all had similar growth rates and anchorage-independent growth abilities and demonstrated similar tumorigenic potential. These findings suggest that c-erbB-2 is a metastasis-promoting gene for breast cancers that is distinct from other tumor-promoting genes in that the c-erbB-2 gene can enhance the intrinsic metastatic potentials of MDA-MB-435 cells without increasing their transformation abilities.

Animals↗

PubMed1997

Is cryosurgical ablation appropriate for treating hepatocellular cancer?

OBJECTIVE: To examine the feasibility and efficacy of cryosurgical ablation as treatment for patients with cirrhosis with unresectable hepatocellular carcinoma. DESIGN: Retrospective case series. SETTING: A tertiary public hospital and a cancer center. PATIENTS: Twelve patients with cirrhosis with hepatocellular carcinoma (stage II, 2; stage III, 1; stage IVA, 7; stage IVB, 2). INTERVENTIONS: Cryosurgical ablation of all identifiable tumors. Nine patients treated with curative intent were included in the survival analysis, and 3 were treated for palliation. Five patients were treated with preoperative intra-arterial chemoembolization. MAIN OUTCOME MEASURES: Perioperative complications and the effects of tumor stage and chemoembolization were examined. Patient survival and disease-free interval were calculated by life-table analysis. RESULTS: No perioperative deaths occurred and 1 patient had 2 postoperative complications: pneumonia and biloma. The mean survival has been 19 months after cryosurgical ablation and 29 months after diagnosis. Three of the 9 patients treated with curative intent died with recurrence at a mean of 17 months after cryosurgical ablation. Four patients are alive with recurrence at a mean of 19 months after cryosurgical ablation and 38 months after diagnosis. Two patients with stage II disease have no evidence of recurrence 10 and 32 months after cryosurgical ablation. CONCLUSIONS: Cryosurgical ablation is feasible and safe for treatment of hepatocellular carcinoma in patients with cirrhosis. The technique is primarily palliative but may provide a possibility of cure in patients with lower-stage disease.

Adult↗

PubMed1997

Biofeedback is effective treatment for levator ani syndrome.

PURPOSE: The effects of biofeedback (BF) on pain relief and anorectal physiology in patients with levator ani syndrome (LAS) were prospectively studied. METHOD: Sixteen consecutive patients (9 men, 7 women; mean age, 50.1 (range, 39-66) years) with LAS were treated with BF from July 1993 to October 1995. Mean duration of pain was 32.5 (standard error of the mean, 6.7) months. All underwent a full course of BF using a manometric balloon technique. Mean follow-up was 12.8 (standard error of the mean, 2.6) months. Pain score and anorectal physiology tests were administered prospectively by an independent observer before and after BF. RESULTS: After BF, the pain score was significantly improved (before BF: median, 8 (range, 6-10); after BF: median, 2 (range, 1-4); P < 0.02). Analgesic requirements were also significantly reduced (all 16 patients needed nonsteroidal anti-inflammatory drugs (NSAID) before BF; only two patients needed NSAID after BF; P < 0.03). There were no significant changes to the anorectal physiology parameters after BF. To date, there have been no side effects or regressions. CONCLUSION: Although BF had a negligible effect on anorectal physiologic measurements in LAS, it was effective in pain relief, with no side effects.

Anal Canal↗

PubMed1997

Randomized controlled trial of primary fistulotomy with drainage alone for perianal abscesses.

PURPOSE: Primary fistulotomy may be advantageous for perianal abscesses because unlike ischiorectal abscesses, fistulas are more commonly found and can be laid open with full preservation of the external anal sphincters. Therefore, a randomized, controlled trial was conducted to compare primary fistulotomy with incision and drainage alone, specifically for perianal abscesses. METHODS: Fifty-two consecutive patients (43 males; mean age, 40 (standard error of mean, 2) years) with perianal abscesses were randomized to treatment by either incision and drainage (controls; N = 28) or fistulotomy (N = 24). Patients were followed up clinically for a mean of 15.5 (standard error of the mean, 0.7) months. Anorectal manometry was also performed before, six weeks, and three months after surgery. RESULTS: Persistent fistulas developing after surgery were significantly more common after incision and drainage (N = 7; 25 percent) than after fistulotomy (N = 0; P = 0.009). One patient in each group was also found to have a residual abscess, which required repeat drainage. All patients remained fully continent. The anal pressures after incision and drainage and fistulotomy were not significantly different. Operative time, hospital stay, and time for the wound to heal completely were the same in both groups. CONCLUSIONS: Primary fistulotomy at the time of drainage for perianal abscesses results in fewer persistent fistulas and no added risk of fecal incontinence.

Abscess↗

PubMed1997

Ambulatory anorectal manometric findings in patients before and after haemorrhoidectom.

The physiological abnormalities in piles before and after surgery were studied by an ambulatory prolonged anorectal manometric technique. Eighteen consecutive patients (12 men, 6 women; mean age 43.6 [standard error of mean, 3.3] years) with 3 prolapsed irreducible piles were prospectively recruited. Haemorrhoidectomy was performed with excision of 3 piles. The anal and rectal pressures were monitored before and at a mean 7.8 (1.5) weeks after surgery when the wounds had healed, for a mean period of 361.3 (47.8) min. The maximum anal pressures dropped significantly from a mean 325 (15.5) mmHg before to 213 (24.9) mmHg after surgery (P < 0.05). Ultraslow wave activity was clearly identified in 11 of 18 patients (61%) before surgery, but not found on post operative studies. The maximum rectal pressures were also significantly reduced after surgery (196.8 [23.2] mmHg before, 75.5 [10.6] mmHg after; P < 0.05). These findings help to confirm that haemorrhoidectomy leads to changes in the anorectal physiological findings.

Adult↗

PubMed1997

Heart rate, heart rate variability, and blood pressure during perioperative stressor events in abdominal surgery.

STUDY OBJECTIVE: To define the behavior of power spectral heart rate variability (PSHR) during potentially stressful events in the perioperative period, and relate it to changes in blood pressure (BP) and heart rate (HR). DESIGN: Longitudinal clinical study. SETTING: Operating room and recovery suites of a large tertiary care referral center. PATIENTS: 26 ASA physical status I, II, and III patients undergoing elective abdominal surgery. INTERVENTIONS: Anesthesia was induced with thiopental sodium and fentanyl, and maintained with isoflurane/nitrous oxide (N2O)/relaxant or enflurane/N2O/relaxant. The trachea was intubated and intraabdominal surgery was performed. MEASUREMENTS AND MAIN RESULTS: Observations consisted of HR, noninvasive blood pressure, and PSHR. They were made before and after induction of anesthesia, tracheal intubation, and surgical incision, and during maximal surgical stimulation and skin closure. HR and mean arterial pressure (MAP) maxima were also recorded for one hour before and after emergence from anesthesia. PSHR was obtained using a special algorithm and data acquisition system for real time spectral analysis of the instantaneous HRversus time function. The HR power spectrum parameters analyzed were low-frequency (LFA; powerband = 0.04 to 0.10 Hz), respiratory-induced frequency (RFA; powerband = respiratory frequency +/- 0.06 Hz), and the ratio of LFA to RFA. With induction of anesthesia, only RFA power decreased significantly. LFA power reduction became significant only after intubation and continued so until after incision. Immediately after induction, the decline in RFA power (vs. preinduction) was more pronounced when compared with the decline in LFA power (76% vs. 34%; p = 0.01). Hence, the ratio LFA/RFA increased significantly after induction of anesthesia. It was significantly higher than at postintubation, preincision, or skin closure. A significant elevation in LFA, LFA/RFA ratio, and BP occurred with maximal abdominal surgical stimulation. Only preinduction LFA, RFA, and LFA/ RFA ratio were predictive of MAP changes with induction of anesthesia (p = 0.006). In 8 of the 15 patients who had MAP changes of at least 10 mmHg with induction, PSHR indices correctly predicted a change of this magnitude. Late intraoperative HR maxima were positively correlated with the change in HR and incision (r2 = 0.58; p < 0.01). The change in BP with incision was positively correlated with early postoperative HR maxima (r2 = 0.60; p < 0.01). CONCLUSIONS: On anesthetic induction, preoperative, but not intraoperative, spectral indices were predictive of BP changes. Power spectral analysis of HR may provide information about the autonomic state that is not evident from BP or HR. The HR power spectrum, in particular, indicated a striking autonomic imbalance immediately after the induction of anesthesia despite stable HR and BP. LFA and LFA/RFA ratio appeared to track sympathetic autonomic activation during abdominal surgical stimulation, but not during other perioperative stressor events.

Abdomen↗

PubMed1997

Increment of hFIX expression with endogenous intron 1 in vitro.

This paper probes into the feasibility of increasing expression level of hFIX gene with endogenous intron 1 sequence. hFIX minigene was obtained with middle sequence truncated intron 1 inserted into the relative site of hFIX cDNA, and plasmid vector pKG5i'IX, retroviral vector GINaCi'IX were constructed. These vectors were transduced into target cells of PA317, C2C12, primary rabbit skin fibroblasts (RSF) and primary human skin fibroblasts (HSF). The expression level of mixed colonies are PA317/pKGoi'IX, 151 ng/10(6) cells/24h; PA317/G1NaCi'IX, 308 ng/10(6) cells/24 h; C2C12/G1 NaCi'IX, 188 ng/10(5) cells/24 h; RSF/G1NaCi'IX, 1929 ng/10(5) cells/24 h; HSF/G1NaCi'IX, 1646 ng/10(6) cells/24 h. These results indicated that hFIX minigene with intron 1 is able to increase the expression level to about 3 times of that of hFIX cDNA. Meanwhile, in order to study the application of hFIX minigene in the retroviral-mediated gene transfer system and refrain from intron splicing during viral production, a retroviral vector G1NaCi'IXR with reversely inserted hFIX minigene expression cassette was constructed. The expression level of reverse constructor in PA317 cells was 390 ng/10(6) cells/24 h with 79% of bioactivity. PCR detection of HT/G1NaCi'IXR cells infected with PA317/G1NaCi'IXR supernatant confirmed the existence of intron 1 sequence. These results suggested that expression vector with forward-inserted intron1-carrying hFIX expression cassette can be used in directed gene transfer, but when using the retroviral-mediated gene transfer system, reversely-inserted intronl-carrying hFIX expression cassette should be considered.

Animals↗

PubMed1997

Presence of inflammatory mediators in the tears of contact lens wearers and non-contact lens wearers.

The present studies have demonstrated the levels of N-methyl histamine in tears from normal physiological states, pathological states and contact lens wear. Histamine was significantly increased in closed eye tears compared with both open and reflex tears. Tears from other ocular conditions had low levels of histamine except for environmental hypersensitivity, which contained significantly elevated levels compared to normal tear types. Interestingly, tears from asymptomatic contact lens wearers had significant levels of histamine whereas tears from contact lens adverse events had lower levels, possibly reflecting a change in histamine metabolism.

Analysis of Variance↗

PubMed1997

Laparoscopic-assisted compared with open total colectomy in treating slow transit constipation.

BACKGROUND: Total colectomy is the procedure of choice when slow transit constipation (STC) can be confidently diagnosed. A laparoscopic-assisted technique (LTC) may be potentially advantageous over traditional open technique (OTC) in the treatment of this benign condition. METHODS: A historical control (non-randomized) study was performed on patients diagnosed to have STC after clinical, anorectal physiologic and transit marker studies. All earlier consecutive patients underwent OTC and the latter consecutive patients underwent LTC. The intra-operative time, blood loss, postoperative ileus recovery, duration of hospitalization and complications were recorded. A bowel function and patient satisfaction questionnaire was administered on follow-up. RESULTS: Twenty-four of 411 patients were found to have STC; 17 (2 men, 15 women; mean age, 40 (standard error of mean [SEM] 5) years) underwent OTC and 7 (2 men, 5 women; mean age, 39.5 (SEM 6) years) underwent LTC. There were significant improvements in the stool frequency, need for assisted evacuation and abdominal distension (P < 0.05) after both procedures; 96% were fully satisfied with the resulting bowel function. However, OTC patients were less satisfied with the cosmetic outcome (P < 0.05). Intra-operative time for LTC was longer by a mean 74 min (P < 0.05). Postoperative blood loss, recovery of ileus and hospitalization time were the same in both groups. There were no deaths. The complication rates were 43% for LTC and 24% for OTC. The predominant complication was bowel obstruction for which two patients (both OTC) required adhesiolysis. CONCLUSIONS: Both OTC and LTC improve bowel function for STC;LTC gives a better cosmetic result, but takes longer to perform.

Adult↗

PubMed1997

Association of ventricular arrhythmias with left ventricular remodelling after myocardial infarction.

OBJECTIVE: To assess the relation between ventricular arrhythmias after myocardial infarction and left ventricular remodelling. DESIGN: Prospective study with consecutive patients. METHODS: 97 patients with acute myocardial infarction underwent serial echocardiographic examinations (days 1, 2, 3, and 7, and after 3 weeks) to determine end diastolic volume, end systolic volume, and ejection fraction; volumes were normalised for body surface area and expressed as indices. Holter monitoring was performed on the day of the final echocardiogram. Coronary angiography was performed in 88 patients before hospital discharge. RESULTS: Complex ventricular arrhythmias (defined as Lown class 3-5) were found in 16 of 97 patients. In logistic regression models, variables predictive of complex ventricular arrhythmias were end systolic volume index on admission (b = 0.054, P = 0.015) and end diastolic volume index after three weeks (b = 0.034, P = 0.012). Complex arrhythmias were also related to the increase of end diastolic and end systolic volume indices throughout the study (F = 5.62, P = 0.046, and F = 6.42, P = 0.017, respectively by MANOVA). A two stage linear regression model of ventricular volume versus time from infarct showed that both intercept (initial volume) and slope (rate of increase) were higher for patients with complex arrhythmias in both diastole and systole (P < 0.001 for all). CONCLUSIONS: Complex ventricular arrhythmias after myocardial infarction are related to the increase of left ventricular volume rather than to depressed ejection fraction. Complex arrhythmias may be an aetiological factor linking left ventricular remodelling with higher mortality, but larger follow up studies of patients with progressive left ventricular dilatation after myocardial infarction are necessary to answer these questions.

Aged↗

PubMed1997

Quantitation of intratumoral thymidylate synthase expression predicts for disseminated colorectal cancer response and resistance to protracted-infusion fluorouracil and weekly leucovorin.

PURPOSE: Response rates to fluorouracil (5-FU)-based therapy remain low. As new, active agents are being tested, information regarding specific intratumoral genetic determinants of chemotherapy sensitivity or resistance can be used to plan therapy rationally. Intratumoral thymidylate synthase (TS) quantitation may be among the most important determinants of sensitivity or resistance to 5-FU. MATERIALS AND METHODS: Forty-six disseminated colorectal cancer patients had measurable tumor biopsies for polymerase chain reaction (PCR)-based determination of TS mRNA pretreatment. Protracted infusion of 5-FU 200 mg/m2/d for 21 days with weekly intravenous leucovorin 20 mg/m2 each cycle was given. After two cycles, responses were evaluated. Response data were correlated with independently determined intratumoral ratios of TS/beta-actin mRNA for each patient. RESULTS: TS/beta-actin ratios were successfully obtained for 42 patients (91%). TS/beta-actin ratios ranged from 0.3 x 10(-3) to 18.2 x 10(-3) (median, 3.5 x 10[-3]). Twelve patients (26%) responded to treatment (median TS/beta-actin ratio, 1.7 x 10[+3]). Thirty-four patients did not respond (median TS/beta-actin ratio, 5.6 x 10[-3]). No patient with a TS mRNA level greater than 4.1 x 10(-3) responded. The median TS/beta-actin ratio (3.5 x 10[-3]) significantly segregated responders from nonresponders (P = .001). Median survival for patients with TS/beta-actin ratios < or = 3.5 x 10(-3) was 13.6 months; for patients with TS/beta-actin ratios greater than 3.5 x 10(-3), it was 8.2 months (P = .02). CONCLUSION: For this cohort, the intratumoral TS/beta-actin ratio had a statistically significant association with response and survival. This relationship for other 5-FU schedules remains unknown. Confirmation of these data in a larger patient population could lead to determination of therapy for disseminated colorectal cancer based on a specific intratumoral molecular parameter.

Actins↗

PubMed1997

Phase II study of liposomal doxorubicin in refractory ovarian cancer: antitumor activity and toxicity modification by liposomal encapsulation.

PURPOSE: A phase II study of liposomal doxorubicin was conducted in patients with ovarian cancer who failed to respond to platinum- and paclitaxel-based regimens. Liposomal doxorubicin was selected as a result of its superior activity against ovarian cancer xenografts relative to free doxorubicin and activity in refractory ovarian cancer patients that was noted during the phase I study. PATIENTS AND METHODS: Thirty-five consecutive patients were accrued in two institutions (22 in one and 13 in the other). All had progressive disease after either cisplatin or carboplatin and paclitaxel, or at least one platinum-based and one paclitaxel-based regimen. Patients received intravenous (I.V.) liposomal doxorubicin 50 mg/m2 every 3 weeks with a dose reduction to 40 mg/m2 in the event of grade 3 or 4 toxicities, or a lengthening of the interval to 4 weeks (and occasionally to 5 weeks) with persistence of grade 1 or 2 toxicities beyond 3 weeks. RESULTS: Nine clinical responses (one complete response [CR], eight partial responses [PRs]) were observed in 35 patients (25.7%), with seven of these having been confirmed by two consecutive computed tomographic (CT) measurements. The median progression-free survival was 5.7 months with an overall survival of 1.5 to 24+ months (median, 11 months). Although 13 patients experienced grade 3 or 4 nonhematologic skin and mucosal toxicities (either hand-foot syndrome or stomatitis), with dose modifications, the treatment was very well tolerated. Nausea that was clearly attributable to the drug, hair loss, extravasation necrosis, or decreases in ejection fraction did not occur. CONCLUSION: Liposomal doxorubicin has substantial activity against ovarian cancer refractory to platinum and paclitaxel. The responses achieved with liposomal doxorubicin were durable and maintained with minimal toxicity. This liposomal formulation should be evaluated further in combination with other drugs in less refractory patients.

Aged↗