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Biomedical subjects

A G Wile

Publications and source records attributed to A G Wile.

At least 19 recordsLinked to original sources
PubMed1995

Replacement therapy for breast cancer survivors. A pilot study.

BACKGROUND: Traditionally, breast cancer survivors were not considered as candidates for hormone replacement therapy (HRT) because of the possibility that an occult metastatic site of disease might be activated, thus negatively influencing the outcome for the patient. METHODS: A retrospective review of 77 breast cancer survivors who have taken HRT was conducted. RESULTS: Seven recurrences were reported among the 77 patients studied in-depth, with correlations to stage, age, and node and receptor status. There have been no recurrences among the 33 additional patients who were placed on the study after the completion of this analysis. CONCLUSIONS: No significant adverse outcome was detected in this group of breast cancer survivors receiving HRT. Given the established benefits of HRT, a reappraisal of this subject is necessary, and a prospective randomized trial is essential.

Adult↗
PubMed1995

Surgical management of breast masses in pregnant women.

OBJECTIVE: The goal of this study was to review the outcomes of breast biopsies in pregnant women in order to plan optimum management strategies for pregnant women with breast masses. STUDY DESIGN: From January 1990 to October 1992, 17 pregnant women underwent breast biopsy at a university hospital. Parameters evaluated were (1) trimester at presentation, (2) timing of biopsy, (3) mode of anesthesia, (4) requirements for tocolytics, and (5) histology of the lesion. RESULTS: Antepartum biopsy was performed on all 11 patients who presented in the first or second trimester. Biopsy was accomplished postpartum in four of five patients presenting in the third trimester. Only one patient required tocolysis (associated with biopsy followed by immediate mastectomy). Histologic diagnosis was predominantly lactating adenoma (13 of 17 patients). CONCLUSION: These results demonstrate that breast biopsy can be safely performed on pregnant women. We recommend that women presenting with breast masses in the first or second trimester undergo antepartum biopsy. We recommend postpartum excision for masses presenting in the latter half of the third trimester. For those presenting in the first half of the third trimester, fine needle aspiration biopsy may be a suitable alternative, particularly for the mass suspicious for cancer.

Adenoma↗
PubMed1993

Intraperitoneal cisplatin with sodium thiosulfate protection in rats with intestinal anastomoses.

Intraperitoneal (IP) cisplatin administered at the time of intraabdominal malignancies such as gastric cancer may prevent or delay intraabdominal recurrence. Perioperative IP cisplatin raises concerns regarding systemic toxicity and retardation of wound healing. Systemic cisplatin toxicity may be reduced by administering its antidote, sodium thiosulfate (STS). A preclinical study of IP cisplatin in rats undergoing a small intestinal anastomosis was carried out. All animals that had received only cisplatin died in the postoperative period as a consequence of cisplatin toxicity. Tensile strength of the intestinal anastomoses was determined on the tenth postoperative day in the surviving animals. Animals that had received intravenous (IV) cisplatin with STS had significantly lower tensile strengths than both those receiving IP cisplatin with STS and STS alone. This study demonstrates the safety of perioperative cisplatin with STS protection by the avoidance of systemic toxicity and minimizing the cisplatin-related retardation of wound healing.

Anastomosis, Surgical↗
PubMed1993

Hormone replacement therapy in previously treated breast cancer patients.

We report our experience with 25 women previously treated for breast cancer who subsequently received hormone replacement therapy (HRT) for the relief of menopausal symptoms and the prevention of postmenopausal cardiovascular disease and osteoporosis. Two patients had in situ disease, 13 had stage I disease, 7 had stage II disease, 1 had stage III disease, and 2 had invasive cancer of undetermined stage. Seventeen patients (group I) began HRT less than 24 months after primary breast cancer therapy, and 8 patients (group II) began HRT more than 24 months after breast cancer therapy. The HRT-free interval for group I patients averaged 7.9 months and for group II patients averaged 64.5 months. The average period of observation while receiving HRT for the entire group was 35.2 months (range: 24 to 82 months). Three of 25 patients have had a recurrence, all in group I. One patient developed local recurrence after breast conservation treatment, and her condition was salvaged by further wide excision. Two patients developed recurrence after mastectomy, and one patient ultimately died of systemic disease. The overall survival rate for the entire group was 96%. Overall survival of high-risk group I patients, with a mean follow-up of 30.4 months, was 94%. We recognize that this report of HRT in a small group of patients does not have the power to demonstrate an adverse effect of HRT on breast cancer. However, the lack of an obvious adverse effect of HRT in this group of breast cancer patients and the known beneficial effect of HRT on postmenopausal cardiovascular disease and osteoporosis warrant formal prospective trials of HRT in such patients.

Adult↗
PubMed1993

The contributions of patient factors, physician delay, and tumor biology to the outcome of gastric cancer.

Patients with gastric cancer were presenting at advanced stage to our hospital. We were concerned that patient or physician controlled factors might have been responsible. A retrospective review of 49 analytic gastric cancer cases presenting to UCIMC between 1984 and 1989 was conducted. Twenty-four patients were determined to have gastric cancer as outpatients, with a median duration of symptoms of 4 months. The other 25 patients had initial physician contact in the emergency room, with a median duration of symptoms of only 1.5 months (P = 0.007). Minority ethnic groups were urgently admitted more frequently than Caucasians (P = 0.004). Multivariate analysis revealed that the worst prognostic factors for gastric cancer were urgent admission of Caucasians and Asians (P = 0.0013) and distant metastases (P = 0.005). Age, gender, duration of symptoms, and physician delay, could not be shown to have any effect on survival. This study demonstrates that the aggressive nature of gastric cancer, particularly in certain minority ethnic groups, is the overriding prognostic feature.

Adenocarcinoma↗
PubMed1991

Increased cisplatin tissue levels with prolonged arterial infusion in the rat.

Prolonged arterial infusions of cisplatin (DDP) have been effective in the treatment of regionally confined malignancies. It is unclear whether the route or schedule of DDP administration was responsible for the observed therapeutic benefit. To resolve this issue, tumor and normal tissue platinum (Pt) levels were determined in rats bearing hind-limb rat mammary tumors after intravenous (IV) and intra-arterial (IA) DDP infusions of constant dose and varying lengths. Infusions of DDP at 6 mg/kg were conducted IA over 30 minutes, and 3, 6, 24, and 48 hours and IV over 30 minutes and 48 hours. After infusion, Pt concentrations in solubilized tissue homogenates were measured by flameless atomic absorption spectroscopy. Maximum tumor Pt levels were seen after 48-hour IA infusion (29.3 micrograms Pt/mg tissue). IA infusions of 24 hours or less resulted in significantly lower Pt levels. Maximum tumor Pt concentration after IV administration was only 0.98 micrograms/mg tissue (48-hour infusion). Muscle Pt levels adjacent to the tumor were highest in the IA infused extremities, but at the 48-hour interval, were 53-fold less than tumor levels. Tumor and adjacent muscle Pt levels were not significantly different from each other after IV administration. This study provides pharmacologic evidence that lengthening the duration of IA DDP infusion increases tumor levels of Pt over that of IV or rapid IA administrations. The benefit of prolonged IA DDP infusions is dependent upon both route and schedule of drug administration.

Animals↗
PubMed1990

Murine monoclonal antibodies to human pancreatic cancer: specificity and sensitivity.

Pancreatic carcinoma (n = 7), pancreatitis tissue (n = 4), normal pancreas tissue (n = 5), colonic adenocarcinoma (n = 4) and in vitro human pancreatic cancer cell lines (n = 6) were studied with the murine monoclonal antibodies (MAbs) 3DS2A, AR1-28, AR2-20, Ca19-9 and CA17-1A to determine their immunohistologic specificity and sensitivity for use as radiolabeled diagnostic imaging agents. Using the avidinbiotin-immunoperoxidase staining technique, MAbs 3DS2A and AR1-28 stained 86 and 100% of pancreatic cancer specimens, respectively. MAbs 3DS2A and AR1-28 are suitable agents for use as radiolabeled diagnostic imaging agents in patients with pancreatic cancer.

Adenocarcinoma↗
PubMed1989

Hormones and breast cancer.

Patients with successfully managed breast cancer have generally been denied subsequent exposure to increased levels of estrogen (endogenous or exogenous) based on the belief that exacerbation of the cancer would occur. The advent of oral contraceptives, the trend toward childbearing later in life, and the demonstration of the protective value of menopausal estrogen replacement therapy against osteoporosis and cardiovascular disease requires that this issue be reexamined. New information bearing on this subject includes the recognition of estrogen receptors, the isolation of youth rather than pregnancy as the factor resulting in poor prognosis, epidemiologic studies showing no increased risk of breast cancer in women using oral contraceptives or taking hormonal replacement therapy, the beneficial effect of pregnancy subsequent to successfully managed breast cancer, and the absence of an adverse effect of oral contraceptives upon established breast cancer. In view of the lack of evidence relating estrogen to exacerbation of existing breast cancer, it may be in the best interest of our patients to liberalize our attitude to renewed hormonal exposure in patients with successfully managed breast cancer.

Breast Neoplasms↗
PubMed1988

Combination cytotoxic chemotherapy with cisplatin or doxorubicin and photodynamic therapy in murine tumors.

This study was designed to evaluate the interaction of photodynamic therapy (PDT) and chemotherapy in an animal model. PDT is based on the interaction of hematoporphyrin derivative and red light of the appropriate wavelength (630 nm) and intensity. Two tumor models were utilized: C3H/Km mice bearing the RIF-1 tumor and BALB/c mice bearing the EMT-6 tumor. Tumor-bearing mice were treated with either cisplatin (DDP), doxorubicin (ADM), PDT, or a combination of drug and PDT. It was demonstrated that the RIF-1 tumor was sensitive to DDP and insensitive to both PDT and ADM. There was no additional antitumor effect when either drug was combined with PDT. The EMT-6 tumor was moderately sensitive to PDT and mildly sensitive to both DDP and ADM. Although the addition of DDP did not potentiate tumor destruction, the addition of ADM significantly enhanced the effect of PDT (P = .01). The enhanced activity of the combination of PDT and ADM appeared to be the result of increased activity of ADM alone, when illuminated with red (630 nm) light. This potentiation may be due to a photochemical process or may be secondary to the mild hyperthermia generated by illumination with the laser. This study demonstrates that PDT combined with cytotoxic chemotherapy is well tolerated in these animals and that certain combinations of PDT and chemotherapy may result in an enhanced tumoricidal effect.

Animals↗
PubMed1988

Plasma ultrafiltration as successful therapy of rabbit VX-2 carcinoma.

It has been demonstrated that tumor-bearing animals elaborate a low molecular weight (less than 10,000 daltons) factor capable of inhibiting in vitro lymphocyte function. It was postulated that removal of this factor would have a favorable effect on host immune response that would translate into improved tumor control. A study was conducted in rabbits bearing the VX-2 carcinoma. Ultrafiltration (UF) was performed 10 days following IV tumor inoculation. UF was achieved by passing blood through an Amicon Diafilter (molecular weight cutoff 10 kD) positioned between the arterial and venous cannulae after heparinization. Two plasma volumes of ultrafiltrate were removed with continuous saline replacement. Two groups of animals received the nonspecific immunoadjuvant, Detox, at time of therapy. Survival in the UF group (N = 9) was compared to untreated tumor-bearing animals (N = 10), sham-operated animals (N = 6), animals receiving Detox (N = 7), and animals receiving UF plus Detox (N = 6). UF imparted a survival advantage when compared to controls (mean 35 days vs. 25 days, P less than .01). The sham group had survival identical to controls. Detox alone conferred minimal survival advantage (mean 29 days, P greater than .05). However, UF + Detox demonstrated maximal survival benefit (mean 40 days, P less than .01). We conclude that UF is an effective anticancer modality in this preclinical model. This study suggests that efforts aimed at eliminating suppressor molecules in cancer patients may be of benefit, especially when combined with biological response modifiers such as Detox.

Adjuvants, Immunologic↗
PubMed1988

Heterogeneity of soluble suppressor factors in rat malignant ascites.

A study was undertaken to enumerate and partially characterize soluble factors generated by tumor-bearing animals capable of suppressing PHA-induced splenocyte proliferation. Sprague-Dawley rats were induced to form malignant ascites by the intraperitoneal injection of the Walker 256 carcinoma. Intact ascites suppressed splenocyte proliferation by 96%. Molecular sieving of the ascites by means of ultrafiltration (10-kilodalton particle cutoff) revealed suppressor activity to reside in both the ultrafiltrate and retentate. Further enumeration of suppressor factors was achieved by preparative polyacrylamide gel electrophoresis of the ascites ultrafiltrate and retentate. Five discrete bands of suppressor activity were resolved in the ultrafiltrate, three of which were heat-labile. Three discrete bands of suppressor activity were resolved in the retentate, none of which were heat-labile. This study underscores the complexity and heterogeneity of soluble factors elaborated in a cancer-bearing animal.

Animals↗
PubMed1987

Pharmacokinetics of hexamethylmelamine in intralipid following hepatic regional administration in rabbits.

Hexamethylmelamine (HMM) is a cytotoxic agent demonstrated to have broad antitumor activity. Poor solubility in aqueous media has precluded significant evaluation of parenteral administration of this drug. A formulation of HMM dissolved in Intralipid has demonstrated excellent tolerance following parenteral administration. The goal of this study was to evaluate the pharmacology of HMM in Intralipid following hepatic regional administration. The routes of administration were intraarterial via the hepatic artery with and without arterial occlusion, i.v. via the portal and jugular veins, and i.p. All animals received a total dose of 10 mg HMM/kg of body weight. Hepatic extraction of HMM was most evident via the portal vein (PV) route [AUC(PV)/AUC(i.v.) = 0.5; P less than 0.05]. Lower plasma levels and areas under the curve (AUCs) were observed for the hepatic artery and hepatic artery-stop flow groups when compared to i.v., but the difference was not significant. Administration i.p. yielded low plasma levels but a very long half-life (88 min). Hepatic tissue levels were highest in the group receiving HMM by the hepatic artery-stop flow route. We conclude that the HMM-Intralipid mixture is well tolerated, that HMM is extracted to a significant degree by the liver following PV administration, and that an i.p. installation of HMM-Intralipid results in prolonged plasma drug levels. This preclinical study supports further efforts at evaluation of parenteral administration of the HMM-intralipid mixture.

Altretamine↗
PubMed1987

The pharmacokinetics of cisplatin in experimental regional chemotherapy.

Cisplatin (DDP) is attractive for use in regional chemotherapy because of its tendency for protein binding. A study of regional chemotherapy was conducted in rabbits bearing the VX-2 carcinoma. Modes of therapy examined were intravenous (IV), intra-arterial (IA), IA with stopflow, IA with outflow occlusion, and isolation-perfusion (I-P). Each mode was evaluated by examining the pharmacokinetics of DDP in systemic and regional administration and measuring tissue concentrations of DDP. It was observed that the systemic exposure to DDP was significantly less for IA with outflow occlusion and I-P when compared to IV, IA, or IA with stopflow occlusion (P = 0.003). Tumor concentrations were highest with IA infusion with outflow occlusion (P = 0.002) and IA stopflow occlusion (P = 0.03). Tumor tissue concentrations were always higher than adjacent muscle DDP concentrations. The authors conclude that significant pharmacologic advantage can be demonstrated for certain modes of DDP administration in this rabbit model, and that these promising results should be followed by clinical trials.

Animals↗
PubMed1987

Sequential elaboration of lymphocyte-enhancing and -suppressing factors in the sera of tumor-bearing animals.

Serum-mediated impairment of lymphocyte function was studied in an animal model. Sprague-Dawley rats inoculated intraperitoneally or subcutaneously with the Walker 256 carcinoma underwent sequential sampling of blood. The effect of these serum samples upon phytohemagglutinin-induced blastogenesis of normal rat splenocytes was monitored in an assay utilizing incorporation of (3H)-thymidine. The effect of serum samples from both the subcutaneously and the intraperitoneally inoculated tumor-bearing animals was biphasic. Early on, serum enhanced blastogenesis and later suppressed blastogenesis. Separation of sera into high and low molecular weight components by ultrafiltration demonstrated the enhancing activity to reside in the high molecular weight fraction. The enhancing activity of sera decreased over time from tumor inoculation. Conversely, suppressor activity increased over time from tumor inoculation. This study demonstrated that suppressor activity of sera obtained from animals with advanced tumors is the result of the lack of enhancing activity coupled with the elaboration of suppressor activity.

Animals↗