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T S Ravikumar

Publications and source records attributed to T S Ravikumar.

At least 19 recordsLinked to original sources
PubMed1996

Expression of 32-kDa laminin-binding protein mRNA in colon cancer tissues.

Colorectal cancer initiation and progression are associated with stepwise genetic alterations. We and others have shown that a gene encoding for a 32-kDa putative laminin-binding protein (LBP-32) is overexpressed during colorectal cancer progression by Northern blots analysis. Northern blots cannot indicate the heterogeneity of expression from cell to cell and the distribution pattern of gene expression within a given tumor. In order to overcome these problems, we examined the LBP-32 mRNA expression in colorectal carcinomas by in situ hybridization. LBP-32 mRNA expression in 30 cases of primary and metastatic colorectal cancers and their respective adjacent normal tissues were detected by in situ hybridization using 35S-UTP radiolabeled antisense riboprobes. The results showed that LBP-32 mRNA was expressed at a low level in the normal colonic mucosa adjacent to the tumor compared with colon cancer tissues. Its expression in poorly differentiated colorectal cancer was much higher than that in well- and moderately differentiated colorectal cancer. More importantly, the LBP-32 mRNA was expressed more highly in the invasive lesions of the cancer and liver metastases compared with the cancer lesions in situ. Our results imply that in situ hybridization is a powerful tool in evaluating the changes in gene expression in the cancer cells and LBP-32 mRNA expression is related to progression, invasion, and metastasis of colorectal cancer.

Carcinoma↗
PubMed1996

Laparoscopic staging and intraoperative ultrasonography for liver tumor management.

Intraoperative ultrasonography has become an invaluable tool for programs that perform large volume, complex liver operations. Together with laparoscopy, intraoperative ultrasonography helps in appropriate staging, aids in decision-making, and tailors operations so as to minimize short-term morbidity and optimize long-term benefit.

Decision Making↗
PubMed1996

Interstitial therapies for liver tumors.

A variety of tumor-directed "interstitial" treatments based on physical, chemical, and radiobiologic antineoplastic principles have been investigated for the management of patients with unresectable tumors confined to the liver. Cryosurgery, ethanol injection, and laser photocoagulation are reviewed.

Animals↗
PubMed1996

Isolated liver perfusion for liver metastases: pharmacokinetic advantage?

The pharmacokinetic advantage of a novel system to noninvasively isolate the hepatic venous outflow and infuse high doses of chemotherapy (doxorubicin or 5-FU) is discussed and compared with intravenous infusion and intra-arterial infusion without hepatic venous detoxification. This dose intensification schema may provide new pharmacokinetic and pharmacodynamic principles for the treatment of a variety of tumors metastasizing the liver, including melanoma, sarcoma, and adenocarcinoma.

Adenocarcinoma↗
PubMed1995

Biochemical modulation of 5-fluorouracil with brequinar: results of a phase I study.

Biochemical modulation can increase the efficacy of 5-fluorouracil (5-FU). Pizzorno et al. have previously shown that brequinar, a de novo pyrimidine synthesis inhibitor, enhances the antitumor effect of 5-FU in vivo [Cancer Res 52: 1660-1665, 1992]. On the basis of their data, we conducted a phase I study of brequinar in combination with 5-FU in patients with refractory solid tumors. The initial dose (100 mg/m2) of brequinar was raised in 100-mg/m2 increments in cohorts of three assessable patients. The initial dose of 5-FU was 500 mg/m2, but escalation was allowed in patients who showed no significant toxic reaction. Brequinar was administered over 1 h and 5-FU over 2 h starting 18-20 h after the initiation of infusion of brequinar. Treatments were repeated weekly. Responses were evaluated after 4 weeks (one course) and then every 8 weeks thereafter. Pharmacokinetics of brequinar and determination of plasma uridine levels were performed in at least three patients at each dose level. Of the 25 patients registered in the study, 21 were assessable for toxicity studies. The dose of brequinar was escalated up to 600 mg/m2. In addition, the dose of 5-FU was increased to 600 mg/m2 as a result of a lack of a significant toxic reaction in the first nine patients. No objective responses were observed. One patient developed grade 3 stomatitis, and one developed grade 3 esophagitis at the 400 and 600 mg/m2 dose of brequinar, respectively. Brequinar produced a dose-dependent decrease in plasma uridine levels at doses up to 500 mg/m2. No additional decrease in plasma uridine occurred with higher doses of brequinar, thus suggesting a plateau effect. This observation prompted us to terminate the study before reaching the maximum tolerated dose of brequinar. Our data indicate that brequinar in doses > or = 400 mg/m2 results in significant biochemical modulation. The lack of toxicity seen at these doses of brequinar suggests that the initial dose of the effector agent 5-FU should be increased in future studies.

Adult↗
PubMed1995

Metachronous small-bowel adenocarcinoma in celiac sprue.

Celiac sprue, or nontropical sprue, is associated with an increased incidence of digestive tract malignancy. We report a patient with celiac sprue who developed two primary adenocarcinomas of the jejunum > 2 years apart. The second cancer was asymptomatic and detected by surveillance computed tomography. Small-bowel cancers are unusual, and frequency of follow-up has not been established, so that it is important to have a high index of suspicion for these malignancies in celiac patients with vague gastrointestinal symptoms.

Adenocarcinoma↗
PubMed1994

Unusual inheritance of primary ciliary dyskinesia (Kartagener's syndrome).

Primary ciliary dyskinesia syndrome is characterised by chronic sinusitis, bronchiectasis, and, in 50% of cases, dextrocardia. It is generally believed to be inherited as an autosomal recessive disorder. In this report, we describe a family consisting of a mother and her five male children, the offspring of three different fathers, all of whom have this syndrome. This argues for either an X linked or autosomal dominant pattern of inheritance. Cytogenetic and FISH (fluorescent in situ hybridisation) analyses were done on the mother and one son and were found to be normal.

Adolescent↗
PubMed1994

Percutaneous hepatic vein isolation and high-dose hepatic arterial infusion chemotherapy for unresectable liver tumors.

PURPOSE: This prospective, nonrandomized trial evaluated a percutaneous isolated chemotherapy perfusion approach for treating advanced primary and metastatic liver tumors. Chemotherapy was administered via hepatic artery catheter and hepatic venous blood isolated by a novel percutaneous double-balloon inferior vena cava (IVC) catheter was passed through a detoxification/filtration cartridge in a venovenous bypass circuit. PATIENTS AND METHODS: Among 23 patients enrolled onto the study, 58 procedures were performed on 21 patients. Twelve patients received dose escalations of fluorouracil (5-FU) (1,000 mg/m2 to 5,000 mg/m2), and nine received dose escalations of doxorubicin (50 mg/m2 to 120 mg/m2). Pharmacokinetic studies included drug accumulation in the liver, extraction by detoxification filters, systemic exposure, and alterations of half-life. Each patient received two treatments at 3-week intervals. Those showing stabilization or response received additional treatments. RESULTS: There was a direct relationship between dose and peak concentration of drug entering the hepatic veins. The system functioned efficiently throughout the dose range, with extraction efficiencies ranging from 64% to 91% (P < .001). The hepatic vein drug levels showed a sixfold increase in 5-FU with dose escalation from 1,000 to 5,000 mg/m2, and a twofold increase in dox with dose escalation from 50 to 120 mg/m2 (P < .001, filter-mediated drug extraction). The treatments were accomplished with only an overnight hospital stay and no mortality. The common procedure-related toxicity was transient hypotension (grade I to II), due to catecholamine depletion by the filter. Dose-limiting toxicity (leukopenia) was observed in patients receiving 5-FU at a dose of 5,000 mg/m2 and doxorubicin at a dose of 120 mg/m2. Significant tumor response (> 95% reduction) was obtained in two patients receiving doxorubicin at 90 mg/m2 and 120 mg/m2. CONCLUSION: The use of a double-balloon catheter to isolate and detoxify hepatic venous blood during intraarterial therapy is technically feasible, safe, and allows administration of large doses of intrahepatic chemotherapy at short intervals. This approach should allow new dose-intensification strategies to increase tumor responses in primary and metastatic liver tumors.

Adenoma, Bile Duct↗
PubMed1994

Intraoperative ultrasonography of liver: detection of occult liver tumors and treatment by cryosurgery.

A prospective study of 110 patients undergoing liver surgery was undertaken to evaluate the usefulness of intraoperative ultrasonography (IOUS) and cryosurgery in treating primary and metastatic liver tumors. The diagnoses were colorectal cancer (n = 72), hepatocellular carcinoma (n = 15), ovarian cancer (n = 8), cholangiocarcinoma (n = 4), and other tumors (n = 11). IOUS results were compared with preoperative CT scan angioportography. IOUS detected 37 lesions not seen on CT in 21 patients (19%) and 13 lesions not detected by bimanual palpation in 6 patients (5%). IOUS-assisted cryosurgery was carried out to ablate unresectable liver tumors in 21 patients (19%). At median follow-up of 14 months, 5/21 patients (24%) achieved complete response; 24 and 52% of patients recurred in the liver and systematically, respectively. Thus, IOUS is useful in detecting occult liver tumors and in providing assistance in tumor ablative therapies. Cryosurgery is useful in controlling some of the unresectable liver tumors, but the 76% recurrence rate implies the need for an effective regional and systemic chemo/immunotherapy.

Adult↗
PubMed1993

Ubiquitin-ribosomal protein S27a gene overexpressed in human colorectal carcinoma is an early growth response gene.

One of the extension proteins on the carboxy terminus of ubiquitin was reported as the ribosomal protein S27a. We have cloned a gene which encodes this ubiquitin hybrid protein from a complementary DNA library of a human colon carcinoma cell line. Northern blot analysis of surgical specimens from colon cancer patients showed that these messenger RNA levels were higher in tumor tissue than in adjacent normal mucosa. Furthermore, to investigate the role of this novel ubiquitin hybrid gene in cellular growth control, the responsiveness of this gene to serum growth factors was examined. Within 30 min after serum or 12-O-tetradecanoylphorbol-13-acetate stimulation, its messenger RNA expression in rat fibroblast cells (Rat 1) was increased. Nuclear runoff transcription studies showed that the kinetics of induction of this gene is almost identical to that of protooncogene c-jun or c-fos, the known early growth response genes. Thus, this ubiquitin hybrid gene appears to be a novel early growth response gene overexpressed in human colon cancer and warrants further studies in the pathogenesis of colorectal carcinoma.

Animals↗
PubMed1993

Expression of colorectal carcinoma-associated antigens in colonic polyps.

Immunohistologic techniques were used to study the expression of colorectal carcinoma-associated antigens in colonic polyps and to compare this with expression in the normal colonic epithelium. Forty-nine polyps were studied using monoclonal antibodies to 16 different blood group and differentiation antigens and carcinoembryonic antigen epitopes. With the Lewis(a) antigen and the two epitopes of CEA recognized by 3D6 and COL-4 expression in polyp tissue was the same as that in the normal colon. Five types of alteration of antigen expression in polyps were seen. The blood group antigens A, B, and Lewis(b), which are expressed only on the right side of the normal adult colon, were detected in both neoplastic and nonneoplastic polyps from the distal colon. The Lewis(x) antigen and the antigen epitopes detected by the antibodies COL-12, CA19-9, ME491, and GA73.3 showed an increased frequency of expression in all types of polyps in comparison with the normal colonic epithelium, while H-type 2, ND4, and the antigen epitope detected by CO29.11 showed a slightly decreased frequency of expression in polyp tissue. The X-like antigen which was expressed in only 7% of normal colon specimens showed increased frequency of expression in polyp tissue with significantly greater expression in neoplastic than hyperplastic lesions (P = 0.003). The TAG-72 antigen was detected only in adenomas with severe dysplasia (P = 0.01), correlating well with premalignant histology. These findings have helped us clarify the variation of antigen expression in colonic polyps and allowed us to define which antigens are worthy of further investigation as markers of possible malignant transformation.

ABO Blood-Group System↗
PubMed1993

A new peripherally implanted subcutaneous permanent central venous access device for patients requiring chemotherapy.

PURPOSE: A peripherally implanted central venous access device (P.A.S. Port; Pharmacia Deltec Inc, St Paul, MN) was evaluated for ease of insertion, functionality, acceptance, and complications in patients who required long-term venous access. A hand-held tracking system (Cath-Finder; Pharmacia Deltec Inc) used to determine catheter tip location was also evaluated. PATIENTS AND METHODS: A P.A.S. Port was placed in 47 patients who required long-term intravenous access. The median follow-up duration has been 32 weeks (range, 2 to 112). Total usage has been 2,028 catheter-weeks. The Cath-Finder was used to determine catheter tip location during insertion. Nursing staff and patient satisfaction were polled and functionality and complications were recorded. RESULTS: The device was found to be simple to insert, the procedure well tolerated, and, with one exception, the Cath-Finder accurately predicted catheter tip location. There was a 6.4% incidence of transient phlebitis and a 6.4% incidence of symptomatic axillary or subclavian vein thrombosis. There were no infectious complications. Access was simple in all but two obese patients. The device functioned well in all patients, except three in whom blood aspiration was difficult and two in whom fluid administration was slow. The device was well tolerated by all patients and nursing staff satisfaction was high. CONCLUSION: This device provides a highly acceptable, additional method of implantable, permanent central venous access for chemotherapy patients with a low complication rate. The successful use of the Cath-Finder and minor extent of the procedure may allow this device to be inserted in a clinic procedure room without sedation and fluoroscopy.

Antineoplastic Agents↗
PubMed1992

Ten-year follow-up of breast carcinoma in situ in Connecticut.

Statistics from the Connecticut Tumor Registry from 1979 to 1988 were examined, and individual medical records from 1979 to 1983 were also reviewed. Three hundred nineteen medical records were available for review, documenting 220 cases of ductal carcinoma in situ and 102 cases of lobular carcinoma in situ. In 1979, there were 33 new cases of ductal carcinoma in situ reported to the Connecticut Tumor Registry, representing 1.8% of all breast cancers. There has been a yearly increase in ductal carcinoma in situ, with 200 new cases, or 7.4% of all breast cancers, reported in 1988. Forty-eight (22%) of 217 patients with ductal carcinoma in situ had bilateral breast involvement with ductal carcinoma in situ or an invasive breast cancer. Ten (83%) of 12 mastectomy specimens from patients with ductal carcinoma in situ who presented with nipple discharge demonstrated residual tumor, suggesting a more diffuse involvement. Two of the three reported recurrences involved nipple discharge. Thirty-seven (16.8%) of the 220 patients with ductal carcinoma in situ and six (5.9%) of the 102 patients with lobular carcinoma in situ were diagnosed as having another unrelated cancer. Ongoing clinical trials will direct optimum therapy for patients increasingly diagnosed as having ductal carcinoma in situ.

Breast Neoplasms↗
PubMed1992

Anti-sense RNA of 32-kDa laminin-binding protein inhibits attachment and invasion of a human colon carcinoma cell line.

Tumor invasion and metastasis involves the interaction between tumor cells and basement membrane, which is mediated in part by laminin receptors/laminin-binding proteins. We have reported that a 32-kDa laminin-binding protein (LBP-32) was overexpressed in colorectal cancer at the messenger RNA (mRNA) level and correlated with clinical staging. However, the function of this protein is not yet defined. In this study, we have analyzed the role of LBP-32 in tumor cell attachment and invasion through various basement membrane components. Blockade of LBP-32 synthesis with an anti-sense RNA was utilized in this study. The partial sequence (237 bp) of LBP-32 was inserted into the EMSV33 vector in the sense or antisense direction. Clone A, a poorly differentiated human colon carcinoma cell line, was transfected with EMSV33 alone (control), or EMSV33 with the insert in sense (LBP-S) or anti-sense (LBP-AS) direction using lipofectin. The cell adhesion assays (at 37 degrees C for 75 min) were performed using parental Clone A cells or the transfectants. Specific attachment to wells coated with laminin, fibronectin, or type IV collagen was evaluated. In vitro cell invasion assays were performed using the parental clone A cells and their transfectants to assess the passage through polycarbonate filters coated with matrigel, a reconstituted basement membrane. The results showed that (a) laminin and collagen IV (but not fibronectin) play a role in colon cancer cell attachment to substrata, and (b) anti-sense RNA of LBP-32 inhibits tumor cell attachment and invasiveness in vitro. These findings suggest a role for LBP-32 in colon cancer progression and metastasis.(ABSTRACT TRUNCATED AT 250 WORDS)

Carcinoma↗
PubMed1992

Percutaneous isolated liver perfusion for treatment of hepatic malignancy: preliminary report.

Chemotherapy for primary or metastatic hepatic malignancy is limited by poor tumor response and dose-related systemic toxicity. As an alternative to chemotherapy infusion by vein or by the hepatic artery, the authors have developed a percutaneous technique of isolated liver perfusion that allows the regional delivery of high-dose chemotherapy to the liver with little systemic toxicity. After placement of a hepatic artery infusion catheter, an 18-F double-balloon catheter is placed into the inferior vena cava through the opposite femoral vein. Balloons are inflated above and below the hepatic veins, thus isolating hepatic venous outflow. The effluent passes through fenestrations in the catheter and is pumped through charcoal hemoperfusion filters where the drug is removed. The filtered blood is returned to the patient through the internal jugular vein. Fifteen treatments have been conducted in eight patients in a phase I dose-escalation study with use of 5-fluorouracil (5-FU). While it is premature to assess tumor response to isolated liver perfusion, the data demonstrate that the procedure is safe and is tolerated by patients. Pharmacokinetic studies show a 5-FU extraction of up to 85%, with minimal drug leakage into the systemic circulation. This technique shows potential for improving liver tumor response while decreasing systemic toxicity.

Administration, Cutaneous↗