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T S Ravikumar

Publications and source records attributed to T S Ravikumar.

At least 55 records · Page 3Linked to original sources
PubMed1990

Expression of a Mr 32,000 laminin-binding protein messenger RNA in human colon carcinoma correlates with disease progression.

Cell surface receptors for laminin may play an important role in tumor migration and metastasis. To evaluate laminin receptor/laminin-binding protein expression in human colon carcinoma, surgical specimens of primary colon cancers and liver metastases were examined by blot hybridization of total RNA with a complementary DNA clone which encodes a Mr 32,000 human laminin-binding protein. The mRNA level of the laminin-binding protein was higher in primary colon carcinoma than in adjacent normal colonic epithelium in 20 of 21 cases. In all 6 cases of colon cancer liver metastases, the laminin-binding protein mRNA level was more than 3-fold greater in tumor than in adjacent normal liver tissue. The tumor/normal ratio of this laminin-binding protein mRNA expression in primary colon cancer has significant correlation with Dukes' classification (P less than 0.001). Our results suggest that mRNA expression of the laminin-binding protein may be a marker of human colorectal cancer progression and biological aggressiveness.

Adenocarcinoma↗
PubMed1990

New surgical treatments for recurrent colorectal cancer.

Currently, only two areas of recurrence in patients with colorectal cancer are potentially surgically curable: isolated liver and isolated lung metastases. Regional recurrence from rectal cancer, although probably not resectable for cure, offers an appropriate palliative goal because symptoms in such patients are intolerable. We review several new diagnostic and therapeutic techniques that have allowed wider application of surgical approaches for cure or palliation in patients with recurrent colorectal cancer.

Adenocarcinoma↗
PubMed1990

Alterations of gene expression in human colorectal cancer. Biological implications.

Alterations in gene expression associated with colorectal cancer have been difficult to study because mucosal cell progenitors are not available in culture. We therefore examined specific genes in approximately 100 human colon cancer cell lines using complementary DNA probes and found profound alterations and heterogenity of gene expression in human colorectal carcinoma. Our data imply that understanding human colorectal cancer will not be accomplished by studying one or two oncogenes in a limited number of cell lines or fresh human tissue. More appropriate postulates of transformation to dictate experimental design may include the investigation of proposed three-dimensional structural changes of interface chromatin or other generalized structural relationships that could predispose to an aberrant gene expression program during transformation. Furthermore, focusing on mechanisms of initiation and defining the molecular genetic markers of gastrointestinal mucosal initiation should lead to a more focused set of genetic, rather than epigenetic, mechanisms that underlie oncogenic transformation.

Blotting, Northern↗
PubMed1990

Clinical evaluation of a side entry access port: a novel dual-lumen venous access device.

The initial clinical experience with a low-profile side entry access (SEA) dual-lumen implantable venous access port for cancer chemotherapy administration is summarized in this report. The catheter material is polyurethane. The overall experience in 35 patients in this study was a total of 6,224 patient days, with a mean of 178 days per patient. A variety of chemotherapeutic agents, biologic response modifiers, and antibiotics were administered. In 26% of the patients, the device chambers were in simultaneous use during the treatment period. A 6% incidence of clinical subclavian vein thrombosis was noted. There was no infectious complications. Inconsistencies in blood withdrawal and temporary catheter dysfunction were comparable to other access ports in clinical use. The novel design of this side entry port and the catheter material of low thrombogenicity make this device a good option in patients requiring a low-profile system and dual access. Nursing staff should be made aware of the side entry design and that in-service training for accessing the septum is required in centers where such devices are not routinely used.

Adult↗
PubMed1989

Experimental liver metastasis. Implications of clonal proclivity and organ specificity.

"Spontaneous" lung metastases develop in over 50% of the animals bearing subcutaneous isografts of WB-2054, a rat colon carcinoma. A metastatic variant has been developed by "Fidler" type in vivo selection, yielding 100% lung metastasis. In a five-week assay to test the organ specificity of this lung metastatic variant, however, "experimental" liver and lung metastases could be induced in 100% and 60% of animals on portal venous and intravenous injections, respectively. The results demonstrate selection of a metastatic variant from heterogeneous primary tumor, and suggest at least two interacting mechanisms: (1) mechanical (the anatomy of the blood-borne metastatic pathways) and (2) biologic (factors intrinsic to primary tumor subpopulations that can be selected for metastatic proclivity). In addition, liver metastases were successfully established from colon tumors induced by cecal wall injection of tumor cells. Such a spontaneous liver metastasis model will be useful to study the specific mechanisms involved during metastasis of colon cancer to the liver.

1,2-Dimethylhydrazine↗
PubMed1989

Splenectomy. The treatment of choice for human immunodeficiency virus-related immune thrombocytopenia?

Immune thrombocytopenia is a well-recognized part of the clinical spectrum of infection with the human immunodeficiency virus. From November 1985 to February 1988, 15 patients who were human immunodeficiency virus-positive underwent splenectomy for refractory immune thrombocytopenia. Eight patients had thrombocytopenia only, and 7 others were pancytopenic prior to splenectomy. Three of the 15 patients fulfilled criteria for acquired immunodeficiency syndrome before splenectomy, and acquired immunodeficiency syndrome developed in 5 patients during the follow-up period. The median duration of thrombocytopenia prior to surgical therapy was 6 months. A bone marrow biopsy specimen showed hypercellularity with increased megakaryocytes. All patients had a therapeutic response to splenectomy. Long-term remission from thrombocytopenia/pancytopenia was achieved in 14 of the 15 patients during a follow-up period of 2 to 21 months. Splenectomy can be accomplished with an acceptable morbidity. Pneumonia developed postoperatively in 2 patients, but they did not manifest the characteristic picture of overwhelming postsplenectomy sepsis. They had received vaccinations against encapsulated organisms preoperatively. We conclude that splenectomy provides a durable and lasting response for HIV-related thrombocytopenia. Vaccination for Streptococcus pneumonia and Haemophilus influenzae should be given prior to splenectomy although its efficacy is not clear in this group.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Ras gene activation and epidermal growth factor receptor expression in human colon cancer.

The expression of various epitopes of epidermal growth factor receptor (EGFr) and mutational activations of ras gene product p21 in colorectal primary cancers from 16 patients have been analyzed in this study. Eight noncancerous colons were used as controls. Indirect immunoperoxidase staining was performed using Avidin-Biotin Complex assay. Monoclonal antibodies against carbohydrate and polypeptide epitopes of EGFr and monoclonal antibodies against "wild-type" and "mutant" ras p21 were used as specific probes. There was no specific expression of the polypeptide epitope of EGFr observed in any of the colon cancers or normal colon tissues. Four of the sixteen tumors (25%) expressed the carbohydrate epitope of EGFr. Glycine----arginine mutation and glycine----valine mutation of codon 12 in ras p21 was observed in 40 and 31% of colon cancers, respectively. Although normal colon showed expression of wild-type ras in about half the cases studied, there was no mutational activation of the ras genes. The morphologically adjacent normal colon mucosa in cancer patients expressed varying levels of mutational activation involving the codon 12. The presence of unusual carbohydrates relating to the EGFr and the products of ras gene activation by point mutations in colon cancers may imply a functional role in transformation.

Antibodies, Monoclonal↗
PubMed1989

Hepatic cryosurgery.

Cryoablation of liver metastases from colorectal and neuroendocrine tumors was accomplished in 20 patients using liquid nitrogen delivered through insulated probes. Intra-operative ultrasound was used to detect liver metastases and to monitor freezing and thawing. Tumor response was evaluated by histologic examination, CT, and serum tumor markers. This study established the safety and technical feasibility of hepatic cryosurgery and provided guidelines for treating liver tumors of diverse origins.

Adult↗
PubMed1989

Resection of hepatic metastases from colorectal cancer. Biologic perspective.

During the past decade the results of slightly fewer than 1000 resections of liver metastases from colorectal carcinoma have been analyzed, retrospectively reanalyzed, and reviewed. The following are confirmed conclusions: major liver resection can be performed safely (less than a 5% operative mortality rate); 20% to 25% of these patients are cured; no other regional therapy options have any curative potential. The following caveats are also obvious: most patients who are operated on are not cured; although predictors have been proposed to select patients most likely to benefit from surgery, none is discriminating in and of itself; most therapy questions in this group of patients have not been addressed in any formal way; surgery for isolated regionally recurrent colon and rectum carcinoma remains an important stopgap only until effective systemic therapy is discovered. This review of our own and other single and multi-institutional prospective and retrospective data will be framed by the following questions. (1) Does resection of liver metastases cure patients or simply select those who would have survived in the long-term without any therapy? (2) In the absence of any formalized, properly designed trial, how can one judge the benefit of resection? (3) Why do metastases recur only in the liver? (4) What new therapies should focus on the predominant secondary failure sites in the majority of patients who do not benefit from hepatic metastasis resection?

Colorectal Neoplasms↗
PubMed1989

Prospective comparison of preoperative imaging and intraoperative ultrasonography in the detection of liver tumors.

A prospective evaluation of the accuracy of preoperative computed tomography (CT), ultrasonography (US), and angiography was performed in 54 patients undergoing resection of hepatic neoplasms. The results were compared with surgical findings and intraoperative ultrasonography (IOUS). A total of 167 lesions was seen by means of IOUS, of which preoperative US enabled detection of 127 (76%). In 48 patients CT allowed detection of 91 of 150 lesions (61%), and in 35 patients angiography showed 56 of 107 lesions (52%). When the detection rate is analyzed according to hepatic segment, the greater overall accuracy of preoperative US may be attributed to a markedly better detection rate in lateral segment of the left lobe of the liver. Lesion size also represented a factor, with preoperative US allowing detection of a greater number of small (less than 2 cm) lesions compared with CT. In patients studied with both CT and US, the combined lesion-detection rate increased to 81% in the right lobe and 76% in the left lobe. Because of this we recommend that preoperative assessment include both CT and US evaluation of the liver. IOUS showed 25% to 35% additional lesions compared with preoperative US and CT. More importantly, 40% of the lesions demonstrated by IOUS were neither visible nor palpable at surgery. We recommend that IOUS be considered in all patients in whom resection of hepatic neoplasm is planned.

Angiography↗
PubMed1987

Hepatic cryosurgery with intraoperative ultrasound monitoring for metastatic colon carcinoma.

We utilized cryosurgery with intraoperative ultrasound (IOUS) monitoring in ten patients to treat multiple unresectable hepatic metastases from colorectal carcinoma. The liver was exposed at laparotomy, and tumors were subjected to three cycles of freezing (eight minutes each) and thawing. Freezing was monitored by IOUS, which visualized frozen tumor as a hyperechoic rim with posterior acoustic shadowing. Frozen normal liver appeared hypoechoic after thawing compared with normal unfrozen liver. There were no significant complications. The follow-up ranged from four months to 17 months (median, 7.5 months). Tumor response was documented by pathologic findings (coagulative necrosis), progressive fall of carcinoembryonic antigen levels, and computed tomographic scan evidence of necrosis and shrinkage of tumor. One patient underwent repeated laparotomy five months after cryosurgery and had the frozen lesions resected; there was no residual tumor. This study establishes the technical feasibility and antitumor response of hepatic cryosurgery and the use of IOUS for precise localization and monitoring of cryoablations.

Adult↗
PubMed1987

Effect of 13-cis-retinoic acid on tumor prevention, tumor growth, and metastasis in experimental colon cancer.

The effect of 13-cis-retinoic acid (13-cis-RA) on 1,2-dimethylhydrazine (DMH)-induced colon cancer in male, random bred, Sprague-Dawley (S-D) and inbred Wister/Furth (W/Fu) rats and on isograft tumor growth and metastases in a Brown Norwegian (BN) X W/Fu F1 rat was studied. 13-cis-RA (300 mg/kg diet) was administered to S-D rats 1 week before commencing DMH injections and for the duration of the experiment. W/Fu rats received 13-cis-RA (10 mg/kg weight X 5 days) 6 weeks after DMH injection had begun and monthly thereafter. Primary tumors were detected by serial laparotomy under ether anesthesia in both strains. The time to tumor onset was significantly delayed in treated groups, S-D and W/Fu, P = 0.0339 and 0.0322, respectively (Mantel-Haenszel test), compared with placebo-treated controls. 13-cis-RA (15 mg/kg weight) administered 2 days before and for the duration of isograft tumor growth (DMH 2054, a well-differentiated mucin-producing colon adenocarcinoma that spontaneously metastasized to lung) had no effect on tumor growth or metastasis in the BN X W/Fu F1 rat. The findings suggest that the role of 13-cis-RA is in colon cancer prevention and not in its treatment either in an adjuvant or established setting.

Animals↗
PubMed1986

Targeting of tumor-associated antigens (TAA) in experimental immunotherapy.

We have previously shown the superiority of tumor-associated antigens (TAA) to function as effective immunogens when administered with bilayer membrane vesicles called liposomes. The ability of liposomes to target TAA to host antigen-presenting cells is analyzed here. 1-Butanol extracted TAA from two syngeneic rat colon cancer tumors (WB 2054 and W 1756) was radioiodinated (131I-TAA). Free 131I and 131I-TAA (2.8 X 10(7) cpm and 75 micrograms TAA per rat) were used as tracers, with or without incorporation into liposomes (composition: sphingomyelin, cholesterol, dicetyl phosphate at 70:24:6 molar ratio). Six groups of male rats (BN X WF for WB2054 and Wistar/Furth for W1756, n = 18 each group) were injected iv with either free tracers or the tracers incorporated into liposomes. Whole blood clearance curve was biphasic (half-life alpha = 5 min; half life beta = 12 hr), suggesting a two-compartmental model of distribution. Seven animals from each group were sacrificed at set times (15 min to 48 hr), organs harvested and cpm/g of tissue estimated. Liposome 131I and liposome 131I-TAA were targeted to and retained preferentially in liver and spleen. Four animals from each group were imaged serially using a gamma camera. Matched pair analysis of regions showed persistently higher activity in liver-spleen area when liposomes were used (P less than 0.001). The uptake of radiolabeled antigens by plastic adherent mononuclear cells in liver and spleen was significantly higher when presented with liposomes (macrophage uptake index: liver = 1.65 vs 0.55; spleen = 5.85 vs 1.15; with and without liposomes, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Serum dependent variability in the adherence of tumour cells to surgical sutures.

Five commonly used surgical sutures were tested for their abilities to adhere tumour cells by an in vitro adherence assay. Adherence was quantified in vitro using radiolabelled tumour cells after standard incubation with a set length of the differing sutures. Tumour cells consistently adhered least to Prolene. All suture materials tested adhered significantly more tumour cells than Prolene (P less than 0.002 for chromic and less than 0.0001 for nylon, silk and Vicryl when compared with Prolene, with increasing cell numbers adhering to the sutures tested in that order). These differences in adherence were dependent upon an as yet unidentified macromolecule(s) in serum. All of the suture materials supported tumour growth in vivo after pre-incubation with tumour cells. Rapidity of in vivo tumour growth, however, correlated well with the in vitro tumour adherence characteristics of the different suture materials. The clinical significance of these findings is discussed.

Animals↗
PubMed1984

Characterization of antigenic components from circulating immune complexes in patients with gestational trophoblastic neoplasia.

The authors have studied serial circulating immune complex (CIC) levels in 15 patients with gestational trophoblastic neoplasia (GTN) for several reasons. Gestational trophoblastic neoplasia can easily be followed from presentation to remission, and CIC changes can be compared with changes in human chorionic gonadotropin (HCG) which is a specific and quantitative marker of trophoblastic tumor load. Twelve patients with hydatidiform molar pregnancy presented with normal CIC levels (255 delta OD450 +/- 97, mean SE [standard error]) as measured by our antigen nonspecific polyethylene glycol (PEG) turbidity assay. Only after reduction in tumor load as monitored by a fall in HCG did CIC rise. In contrast, three patients with choriocarcinoma presented with significantly elevated CIC levels (513 delta OD450 +/- 147, P less than 0.05 compared to normals) which slowly declined in parallel with HCG levels following evacuation and chemotherapy. Sera at peak PEG-CIC from three patients with molar pregnancy or choriocarcinoma were precipitated with 3.75% polyethylene glycol to concentrate circulating immune complexes. Circulating immune complex levels were fractionated on Sephadex G-200 in an acid buffer (pH = 2.8). An identifiable antigenic component of the CIC in both diseases was found to be paternal HLA antigen. This was demonstrated by the ability of the latest eluting CIC fraction to inhibit paternal lymphocyte lysis using anti-HLA antisera against the husband's HLA tissue type. In each case, this fraction contained no immunoglobulin or beta-2 microglobulin and was antigenically crossreactive with only one of the husband's HLA haplotypes. The authors believe the PEG-CIC assay has allowed them to define the kinetics of host humoral response in GTN, and has provided a method for recovering immunogenic tumor-associated antigens from these complexes which may apply to other solid tumors.

Antigen-Antibody Complex↗
PubMed1984

Patterns of failure after surgical cure of large liver tumors. A change in the proximate cause of death and a need for effective systemic adjuvant therapy.

During a period of 7 years, we have aggressively treated liver tumors whether primary or metastatic. Our experience after 43 curative major liver resections has shown an excellent overall survival: 34 of 43 patients still alive a median of 12 months after liver resection (patient ages ranged from 21 to 85 years, median 57 years). Nineteen patients underwent right hepatic lobectomy, 9 trisegmentectomy, 5 left hepatic lobectomy, 5 extended left hepatic lobectomy, 4 right lobectomy plus left lobe wedge resection, and 1 patient underwent a major hilar wedge resection. Two patients died from sepsis and hepatic failure on or before the 60th postoperative day. One patient with no evidence of recurrent colorectal cancer was lost to follow-up after 2.5 years. One patient died without cancer 12 months after left hepatic lobectomy for colon cancer metastases. Cumulative survival for the entire series and for patients after resection of colorectal cancer metastases was the same: 1 year survival 90 percent; 2 year survival 75 percent, and 3 year survival 65 percent. Seventeen of 30 patients remain disease-free after resection of liver metastases. Of the 13 who had recurrence, 8 are still alive. Ten recurrences were outside of the residual liver (predominantly multiple pulmonary metastases). One recurrence was in the right hemidiaphragm, and only three were in the residual or regenerated liver. Serial carcinoembryonic antigen analysis was the best indicator of recurrence in these 13 patients, 12 of whom were asymptomatic. These data confirm that major liver resection can be performed with minimum postoperative mortality (4.7 percent in this series). More importantly, the majority of patients were cured of their liver metastases. The next goal should be the initiation of adjuvant systemic therapy trials after liver resection in such patients.

Adult↗
PubMed1984

Renal toxicity of mitomycin-C.

The clinical spectrum and the pathological findings of renal toxicity in four patients treated with mitomycin-C are described. Our experience and evidence in the literature indicates that the renal impairment appears to be total-dose-related, with most patients developing renal symptoms after receiving at least 60 mg of mitomycin-C. The renal morphologic changes reveal a glomerular and vascular process similar to that seen in a number of clinical situations associated with the hematologic findings of microangiopathic hemolytic anemia. In patients with malignant disease, it may be that the use of mitomycin-C either alone or in combination with other drugs causes endothelial vascular damage with resultant activation of the coagulation system. There is evidence that early detection of the renal impairment and withdrawal of mitomycin-C might halt further progression of renal failure.

Adult↗