Biomedical subjects

M H Torosian

Publications and source records attributed to M H Torosian.

At least 37 records · Page 2Linked to original sources

PubMed1993

Effect of tumor burden on futile glucose and lipid cycling in tumor-bearing animals.

Futile cycling of metabolic substrates may play an important role in the development of cancer cachexia. To determine the effect of tumor burden on futile glucose and lipid cycling, 64 female Lewis/Wistar rats were randomized to control (non-tumor-bearing), small tumor burden, or large tumor burden groups (MAC-33 mammary adenocarcinoma). After 5 or 25 days of tumor growth, animals received a 5-day period of parenteral nutrition (158 kcal/kg/day) followed by a 6-hr infusion of the stable isotopes glucose-2-d and glucose-6,6-d2 or [C13]palmitate. The heavy glucose isotopes glucose-2-d and glucose-6,6-d2 are labeled with deuterium at the 2-carbon position and doubly labeled with deuterium at the 6-carbon position, respectively, to obtain differential molecular weights. No increase in glucose or lipid cycling was observed in animals with small tumor burdens. In contrast, a significant increase in plasma rate of appearance (Ra) of glucose-2-d (1377 +/- 136 mg/hr vs 947 +/- 54 mg/hr), Ra of glucose-6,6-d2 (810 +/- 88 mg/hr vs 510 +/- 24 mg/hr), and total glucose cycling (548 +/- 57 mg/hr vs 416 +/- 28 mg/hr) was seen in animals with large tumor burdens compared to control animals (P < 0.05). Although a trend toward increased lipid cycling was seen in tumor-bearing versus control animals, this change was not significant. Thus, futile cycling of glucose was significantly elevated in animals with large tumor burdens and may cause significant energy wasting to contribute to the development of cachexia in the tumor-bearing host.

Adenocarcinoma↗

PubMed1993

Inhibition of tumor metastasis by a circulating suppressor factor.

Increased growth of tumor metastases has been reported after primary tumor excision in animal models. Postulated mechanisms for this phenomenon include circulating suppressor factors secreted by the primary tumor, tumor manipulation during surgical excision, and limiting nutritional factors which are consumed by both primary and metastatic tumors. To study this phenomenon, Lewis/Wistar rats with subcutaneous mammary adenocarcinoma implants (MAC-33) were randomized to receive either a standard protein diet (22.0% protein, 4.20 kcal/g) or a protein-depleted diet (0.03% protein, 4.27 kcal/g) ad lib per os. Twenty-one days after tumor inoculation, half of the animals in each dietary group underwent primary tumor excision. Control animals underwent sham excision on the flank contralateral to the tumor and physical manipulation of the primary tumor. At sacrifice 35 days after tumor inoculation, a significant increase in regional metastasis (axillary lymph nodes) and distant metastasis (lungs) occurred after primary tumor excision in animals receiving the standard protein diet. No increase in regional or distant metastases were found in animals receiving the protein-depleted diet after tumor excision. Serum was collected from animals given the standard protein diet following tumor or sham excision and added to MAC-33 tumor cell cultures for in vitro determination of tumor cell proliferation. [H3]Thymidine incorporation by MAC-33 cells in vitro was significantly suppressed by serum from tumor-bearing animals. These results imply that the biologic mechanism mediating this phenomenon is a circulating suppressor factor of tumor metastasis which is produced in tumor-bearing animals receiving standard protein (but not protein-depleted) diets.

Adenocarcinoma↗

PubMed1993

Recurrent breast cancer: presentation, diagnosis, and treatment.

Patients must be followed up closely after primary therapy for invasive breast cancer so that locoregional recurrences can be detected early. Once a recurrence has been detected, a thorough evaluation is indicated to exclude distant metastatic disease. If none is found, the patient may be a candidate for aggressive surgical intervention to render the patient disease-free. If distant disease is found, certain sites, such as the CNS or long bones, may warrant aggressive therapy because failure to treat these sites may lead to excessive morbidity. In most situations, patients with distant disease are treated with palliative measures. In selected instances, however, patients with metastatic breast cancer are candidates for aggressive intervention, including pulmonary or liver resection or high-dose chemotherapy in combination with autologous bone marrow transplantation, to rid the patient of the disease.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1992

Colon invasion by primary splenic lymphoma: a case report and review of the literature.

Primary splenic lymphoma accounts for 1% of lymphomas. The definition of primary splenic lymphoma is controversial and its clinical presentation is variable. This report describes a patient with primary non-Hodgkin's lymphoma of the spleen with transmural colonic invasion. This unique case represents the first reported instance of splenic lymphoma with histologically demonstrated invasion to the colonic mucosa. The clinical and pathologic features of this case and primary splenic lymphoma in general are reviewed.

Aged↗

PubMed1991

Growth hormone inhibits tumor metastasis.

The effect of growth hormone on tumor growth and metabolism in the tumor-bearing host is unknown. This study was done to determine the effect of recombinant growth hormone on primary tumor growth, tumor metastasis, and carcass weight in tumor-bearing animals. Twenty-seven female Lobund/Wistar rats with subcutaneous prostate tumor implants (PA-III) were randomized to receive a standard protein diet (22.0% protein; 4.27 kcal/g) or an isocaloric, protein-depleted diet (0.03% protein; 4.27 kcal/g) ad libitum orally. One half of the animals in each group were randomized to receive daily injections of either recombinant growth hormone (1000 mU/kg/day intramuscularly) or placebo (saline) for 14 days. A significant increase in body weight was observed in growth hormone-treated animals without acceleration of primary tumor growth. Spontaneous pulmonary metastasis was inhibited significantly in animals in both dietary groups treated with growth hormone. Thus, growth hormone selectively supports host growth and inhibits pulmonary metastasis in this tumor-bearing animal model. The potential metabolic effects and clinical consequences of treating cancer patients with growth hormone is discussed.

Animals↗

PubMed1991

An evaluation of the clinical usefulness of CEA in colorectal cancer.

Carcinoembryonic antigen is the most common tumor marker in use today. Plasma CEA has no role as a screening tool for large patient populations but does correlate with tumor stage, prognosis, and extent of surgical resection for individual patients. Serial monitoring of plasma CEA levels can detect tumor recurrence prior to clinical or radiologic evidence of disease. An elevated or progressively rising post-operative CEA level is a definite indication for surgical reexploration, with the intent to surgically resect locally recurrent or metastatic disease. Finally, anti-CEA antibodies may be used in the future to improve preoperative staging and to treat colorectal carcinoma.

Carcinoembryonic Antigen↗

PubMed1991

Total parenteral nutrition and tumor metastasis.

A major clinical concern with providing total parenteral nutrition to the tumor-bearing host is the potential to stimulate tumor growth. This study was performed to determine the effect of total parenteral nutrition on primary tumor growth and spontaneous pulmonary metastasis in Lobund rats with subcutaneous prostate adenocarcinoma (PA-III) implants. Significant acceleration of primary tumor growth and tumor metastasis occurred in animals receiving parenteral nutrition consisting of amino acids, dextrose, and lipid or standard enteral nutrition compared to control animals. This study represents the first report of stimulating tumor metastasis with specific parenteral nutrients and clearly indicates that both primary tumor growth and tumor metastasis can be altered by exogenous substrate administration.

Amino Acids↗

PubMed1990

Protein intake and 5-fluorouracil toxicity in tumor-bearing animals.

The administration of chemotherapy is limited in clinical situations by lack of selective antineoplastic activity resulting in significant host toxicity. Although it has been suggested that nutrition support can reduce chemotherapy-related toxicity, few controlled studies exist to document this clinical impression. This study was performed to determine the effect of enteral protein intake on 5-fluorouracil toxicity in tumor-bearing animals. Seventy-nine female Lewis/Wistar rats with subcutaneous mammary tumor implants (AC-33) were randomized to receive either standard protein (22.0% protein; 4.27 kcal/g) or an isocaloric, protein-depleted diet (0.03% protein; 4.20 kcal/g). One-half of the animals in each group received daily injections of 5-fluorouracil (15- or 25 mg/kg ip) or placebo (saline) for 4 or 5 days. Standard protein intake significantly increased host body weight and decreased leukopenia at low (15 mg/kg) and high (25 mg/kg) 5-fluorouracil therapy. At high-dose 5-Fluorouracil (25 mg/kg), the incidence and duration of diarrhea were decreased in animals receiving standard protein intake. Thus, enteral protein intake significantly reduced clinical and objective 5-fluorouracil toxicity and improved body weight in this tumor-bearing animal model.

Animals↗

PubMed1989

Tumors--effective nitrogen traps independent of protein intake.

Despite abnormalities in host nitrogen metabolism, animal studies have demonstrated that tumors successfully compete with host tissues for substrates during periods of nutrition support. The present study was performed to determine the effect of protein depletion on protein content of both tumor and host tissues in tumor-bearing animals. Following subcutaneous mammary tumor (AC-33) implantation, 56 female Lewis rats were randomly assigned to one of two nutrient regimens: (1) protein-depleted chow (0.05% protein) or (2) standard rat chow (22.1% protein) ad libitum per os. Animals were sacrificed after 7 or 14 days on each diet and protein content of tumor and three metabolically active host tissues (liver, gastrointestinal mucosa, and bone marrow) was determined. As tumor growth progressed, tumor protein content increased while liver and gastrointestinal mucosa protein content was depleted; no significant change occurred in protein content of bone marrow. These metabolic alterations occurred regardless of protein intake. Thus, tumors are effective nitrogen traps independent of protein intake and despite wasting of normal host tissues (liver and gastrointestinal mucosa).

Animals↗

PubMed1989

Spontaneous small bowel obstruction associated with a spontaneous triplet gestation. A case report.

Spontaneous bowel obstruction in pregnancy is a rare event and usually associated with a prior history of surgical procedures or infection. Its symptoms can mimic physiologic changes in pregnancy or preterm labor. We treated a woman who had a triplet gestation and whose lack of predisposing factors delayed the diagnosis of obstruction. The patient delivered prematurely at 22 weeks and required surgery to alleviate the obstruction. The possibility of intestinal obstruction should be entertained in any pregnant woman presenting with nausea, vomiting and an overdistended uterus.

Adult↗

PubMed1988

Reduction of methotrexate toxicity with improved nutritional status in tumor-bearing animals.

The administration of chemotherapy in clinical situations is limited frequently because of the associated toxicity to normal bone marrow cells, gastrointestinal epithelium, and other host tissues. Although nutritional support has been advocated to reduce chemotherapy-related toxicity in cancer patients, few studies substantiate this clinical impression. The current study was performed to determine the role of nutritional status and enteral nutrient intake as determinants of methotrexate (MTX) toxicity in a well-controlled, tumor-bearing animal model. After subcutaneous mammary tumor (AC-33) inoculation, 56 female Lewis/Wistar rats were assigned randomly to one of the following two nutritional regimens for 14 days: (1) protein-depleted chow (PC) (0.03% protein; 4.27 kcal/g) or (2) standard chow (RC) (22.0% protein; 3.50 kcal/g). After 7 days of dietary control, all animals received one of three weight-adjusted doses of MTX (5, 10, or 20 mg/kg intramuscularly [IM] ) or placebo. All animals received leucovorin rescue (0.6 mg IM) at 6 and 24 hours after MTX injection. Improved nutritional status was associated with a significant reduction in objective measures of MTX-related morbidity and mortality. At low doses of MTX (5 and 10 mg/kg), the mean duration of clinical signs of toxicity (i.e., hair loss, lethargy, and diarrhea) and severity of leukopenia were greater in protein-depleted (PD) animals. With high-dose MTX (20 mg/kg), mortality was increased significantly in PD animals (100%) compared with well-nourished animals (0%). Equivalent tumor response was observed in PD and well-nourished animals. Thus, improved nutritional status by enteral nutrition reduced the morbidity and mortality associated with MTX significantly in this tumor-bearing animal model.

Adenocarcinoma↗

PubMed1988

Soft-tissue sarcoma: initial characteristics and prognostic factors in patients with and without metastatic disease.

Five hundred and sixty-five patients with soft-tissue sarcoma were admitted to Memorial Sloan-Kettering Cancer Center from July 1, 1982 to July 1, 1985. Clinical and pathologic factors were analyzed to identify initial characteristics and to determine factors associated with prognosis and the development of metastasis. In decreasing order of frequency, the most common sites of primary tumor were the extremity (51.1%), retroperitoneum/viscera (28.8%), trunk (15.9%), head and neck (3.7%) and breast (0.4%). The most common histologic types were liposarcoma (21.4%), malignant fibrous histiocytoma (20.2%), leiomyosarcoma (20.0%), fibrosarcoma (11.0%), and tendosynovial sarcoma (9.6%). One hundred and twenty-eight patients (22.7%) had metastases in a median follow-up period of 19 months. Metastasis was more common in patients with retroperitoneal and visceral sarcomas than in patients with extremity sarcomas. Patients with leiomyosarcomas were more likely to develop metastases than those with other histologic types. Fibrosarcoma and liposarcomas were the least likely to develop metastases in this time frame. Tumors greater than 5 cm in diameter occurred more frequently in patients with metastases. Actuarial survival was related to the site of primary tumor and the histologic type and grade of malignancy. Multivariate analysis indicated that patients with low-grade sarcomas, extremity sarcomas, and fibrosarcomas and patients without metastatic disease demonstrated significantly improved survival. In patients with metastases, disease-free interval (less than 365 or greater than or equal to 365 days) was significantly related to overall survival.(ABSTRACT TRUNCATED AT 250 WORDS)

Actuarial Analysis↗

PubMed1988

Effect of TPN on bone marrow kinetics--therapeutic implications.

Stimulation of tumor and host tissue proliferation occurs with nutritional support of the tumor-bearing host. This study was performed to determine the effect of parenteral nutrition on bone marrow cytokinetics in tumor-bearing animals. Forty-three Lewis/Wistar rats with subcutaneous mammary tumor implants (AC-33) were protein-depleted for 8 days, underwent superior vena cava cannulation and were randomized to receive intravenous saline or total parenteral nutrition (TPN). Animals receiving TPN were sacrificed after 2, 6, 12, 24, and 48 hr and bone marrow cells were harvested for cell cycle analysis by flow cytometry. Compared to control animals, a significant increase in bone marrow cells in S (DNA synthetic) phase was demonstrated after 24 hr of TPN. The ratio of sensitive/resistant bone marrow cells to chemotherapy specific for cells actively synthesizing DNA was increased after 24 hr of TPN. This alteration in bone marrow cytokinetics was transient and distinct from the previously documented stimulation of tumor growth kinetics. The potential therapeutic implications of differentially stimulating host tissue and tumor growth kinetics with TPN are discussed.

Animals↗

PubMed1988

Emergency laparotomy for spontaneous intestinal and colonic perforations in cancer patients receiving corticosteroids and chemotherapy.

Thirty patients with lymphoma (12), leukemia (two), myeloma (one), or metastatic solid tumors (15) were explored for 31 episodes of spontaneous intestinal perforation during an 11-year period at Memorial Sloan-Kettering Cancer Center. Twenty-three patients (76.6%) were receiving corticosteroids alone or in combination with chemotherapy and seven patients (23.4%) were receiving chemotherapy alone at the time of perforation. Fourteen perforations (45%) occurred in the small intestine and 17 perforations (55%) occurred in the colon. Malignancy was histologically demonstrated at the site of perforation in 16 patients (52%). Twenty major postoperative complications occurred in 15 patients (50%) and the operative mortality rate was 53%. Factors such as age, sex, duration or type of symptoms, site of perforation, malignancy at the site of perforation, peripheral leukocyte count, and serum albumin and total protein levels were not significantly related to patient survival. Early diagnosis and aggressive surgical intervention is essential to improve survival following intestinal perforation in this high-risk population.

Adrenal Cortex Hormones↗

PubMed1988

The clinical usefulness and limitations of tumor markers.

This state-of-the-art review identifies the clinical usefulness and limitations of currently available tumor markers. The role of specific tumor markers in screening, assessing extent of disease and monitoring the response of the tumor to antineoplastic therapy is discussed. Recent technologic advances, including monoclonal antibodies and genetic analysis, may identify additional tumor markers and provide insight into the developmental process of neoplasia by characterizing the biologic changes associated with malignant disease.

Acid Phosphatase↗

PubMed1987

Liposarcoma of the spermatic cord: case report and review of the literature.

This report describes a patient with liposarcoma of the spermatic cord. The clinical presentation, pathogenesis, and prognosis of this unusual sarcoma are reviewed. The low-grade malignant potential and irregular growth characteristics of this liposarcoma render preoperative diagnosis difficult. The role of radical orchiectomy, retroperitoneal lymph node dissection, radiation therapy, and chemotherapy in the treatment of spermatic cord sarcomas is discussed.

Genital Neoplasms, Male↗

PubMed1987

Colon carcinoma metastatic to the thigh--an unusual site of metastasis. Report of a case.

Metastasis from colorectal carcinoma occurs by either lymphatic or hematogenous spread. The pattern of metastasis in patients with colorectal malignancy has been characterized by numerous clinical, surgical, and autopsy studies. The most common sites of colorectal metastasis are the liver and lung. Only two previous instances of colorectal carcinoma metastatic to skeletal muscle have been reported. The present report documents the third case of colorectal cancer metastatic to skeletal muscle and reviews the typical pattern of distant metastasis from colorectal carcinoma.

Adenocarcinoma, Mucinous↗

PubMed1986

Nutritional support in the cancer-bearing host. Effects on host and tumor.

Cancer patients have the highest prevalence of malnutrition of any group of hospitalized patients. The potential causes of this malnutrition are numerous, as elements of both starvation and stress are evident in the cancer-bearing host. The presence of the tumor alone may lead to reduced intake of nutrients and treatment modalities of surgery, chemotherapy, and radiation therapy further exacerbate nutritional deficits. It is clear that the tumor requires energy substrates to grow, and that these substrates are exacted from the host. Animal studies identify progressive nutritional depletion concomitant with increasing tumor growth during ingestion of a regular diet. This appears predominantly due to reduced dietary intake in addition to host metabolic alterations. In animal/tumor models deliberate dietary protein depletion results in severe host weight loss, but also causes diminished tumor growth rates. Dietary manipulation in these animal/tumor models have demonstrated methods of improving tumor response to chemotherapy by manipulation of tumor growth rates. In addition, drug-pharmacokinetics have been altered by dietary manipulation. However, data from animal/tumor models are not directly applicable to man since the tumor in animals usually results in the death of the host within six to eight weeks. Nevertheless, controlled laboratory studies in animals provide basic metabolic information which promotes understanding of host/tumor relationships in man. In cancer patients malnutrition has prognostic value, leads to a distortion of body composition with erosion of body protein and fat stores, and compromises the delivery of adequate therapy. There is no direct objective evidence of accelerated tumor growth in humans with cancer who receive nutritional support as part of their treatment regimen. The host benefits to the extent that body composition is at least maintained during the period of nutritional repletion. Thus, nutritional support provides support to the patient during periods of treatment and dietary deprivation. No improvement in the tumor's response to therapy, however, has been demonstrated by this approach.

Animals↗