Biomedical subjects

J L Weese

Publications and source records attributed to J L Weese.

At least 19 recordsLinked to original sources

PubMed1992

Conservative management of extensive low-lying rectal carcinomas with transanal local excision and combined preoperative and postoperative radiation therapy. A report of a phase I-II trial.

Between 1986 and 1990, 16 patients were enrolled in a prospective Phase I/II study of transanal local excision and combined preoperative and postoperative radiation therapy (RT). All patients had biopsy-proven adenocarcinoma extending to within 6 cm of the anal verge and involvement of at least one third of the rectal circumference with tumor. Five of 16 patients (32%) had T3 tumors, and only two patients had T1 tumors. Patients received a single 500 cGy fraction of RT to the pelvis within 24 hours before surgery and underwent transanal excision followed by postoperative RT (median dose, 5040 cGy). With a median follow-up of 33 months, overall 3-year actuarial survival was 94%. Two patients had isolated local recurrences (both successfully salvaged), and four had distant metastases but maintained local control. The 3-year actuarial rates of continuous freedom from any relapse, continuous local control, and no evidence of disease at last follow-up were 53%, 80%, and 71%, respectively. Only three of 16 patients required colostomy, resulting in a 3-year actuarial colostomy-free rate of 77%. There was a trend toward a higher rate of relapse (P = 0.066) in patients with T3 tumors than those with T1 and T2 tumors. Sphincter-preserving therapy for low-lying rectal carcinomas using local excision and combined preoperative and postoperative RT is feasible, although improved local and adjuvant therapy is needed for patients with T3 lesions.

Adenocarcinoma↗

PubMed1992

Intratumoral rIL2-based immunotherapy in B16 melanoma.

Limiting factors in systemic recombinant interleukin-2 (rIL2) therapy may be overcome by intratumoral (IT) administration. A series of experiments was conducted to assess the efficacy of IT rIL2 alone and in combination with LAK cells and IFN-gamma. C57BL/6 mice bearing B16-F10 subcutaneous tumors were randomly assigned to treatment groups including: noninjected controls, IT placebo (NaCl, D5W), IT bovine serum albumin (BSA), IT rIL2 (centrally and peripherally), IT rIL2/LAK, IT rIL2/IFN-gamma, and intraperitoneal (IP) rIL2. A tumor size-dependent dose of cytokine was injected daily and LAK cells were given weekly. Systemic immune response was assessed by splenocyte mitogenesis and T-cell subset distribution using thymidine radioassay and flow cytometry, respectively. In terms of survival and tumor growth rate, IT rIL2 was superior to noninjected control, IT placebo, IT BSA, and IP rIL2 (P less than 0.05). The addition of IT LAK cells conferred no therapeutic advantage. The combination of rIL2 and gamma IFN-gamma had a slight survival benefit over rIL2 alone (30.8 days vs 20.4 days). Histologic analysis demonstrated an increase presence of intratumoral macrophages in the IT rIL2-treated tumors (P less than 0.05). Lymphocyte mitogenesis and L3T4+ subset were not altered by any treatment. In vitro thymidine uptake by tumor cells was not affected by rIL2 nor IFN-gamma alone but the combination of rIL2 and IFN-gamma resulted in significant tumor cell growth inhibition. Spontaneous lung metastases were more prevalent following central IT rIL2 (75% vs 29%, P = 0.07) not accountable by needle trauma but avoidable by the use of peritumoral injection.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1991

Lymphokine-activated killer cell suppressor factor in malignant effusions.

We examined the possibility that tumor-released products inhibit lymphokine-activated killer cell activation. Lymphokine-activated killer cells from human peripheral blood lymphocytes were activated with recombinant interleukin 2 for 4 days in the presence of malignant effusions or conditioned media from cultured cell lines (10% vol/vol). Eight of 10 malignant effusions/media suppressed the induction of lymphokine-activated killer cell cytotoxicity, as measured in a 4-hour sodium chromate release assay. Seven of 10 effusions/media inhibited lymphokine-activated killer cell proliferation. Suppression was both dose and time dependent. A representative suppressive effusion was fractionated by agarose gel chromatography, treated with detergents disruptive of ionic bonds and lipids, and refractionated using polyacrylamide gel chromatography. Seven suppressive fractions ranging in molecular weight from 1 x 10(5) to 3 x 10(5) d were isolated. It is speculated that this suppressor factor may represent a large multimeric structure with ionic-bonded individual suppressive components.

Cell Division↗

PubMed1991

Development of lung metastases after curative intraperitoneal chemotherapy in a rat colon cancer model.

A model of colon peritoneal carcinomatosis was developed by injecting 5 x 10(7) viable tumor cells intraperitoneally into Fisher 344 rats. All 40 control rats developed bulky abdominal tumor with ascites and died of peritoneal carcinomatosis and bowel obstruction (median survival 5 weeks). One day after tumor implantation, treatment group rats received a single intraperitoneal injection of single agent or combination chemotherapy. The most active intraperitoneal single agents were 5-fluorouracil, cisplatin, and etoposide. The most active combination was 5-fluorouracil and cisplatin. Combination chemotherapy produced a significant increase in median, 10-week, and 20-week survival (vs control and single agent). Six of 11 (55%) rats treated with intraperitoneal combination chemotherapy dying between 10-20 weeks died of lung metastasis with cure of intraperitoneal tumor. The increased ability of intraperitoneal combination chemotherapy to cure intraperitoneal disease was offset by the development of lung metastasis.

Adenocarcinoma↗

PubMed1991

Contribution of patient history to the glutathione S-transferase activity of human lung, breast and colon tissue.

Overexpression of the glutathione S-transferases (GSTs) and their involvement in the detoxification of anticancer agents has prompted numerous investigations of the enzyme activity of human tumor tissue. This study represents an in-depth evaluation of the contribution of patient history and pathological status to the GST activity of various human tissues. GST activity was elevated significantly in tumors of the lung, breast and colon as compared to unmatched and matched normal tissue from the same organ. The GST activity of primary breast tumors varied significantly with the stage of the tumor. Breast tumors previously treated with both radiation and chemotherapy had significantly lower levels of GST activity than untreated tumors. Neither progesterone nor estrogen receptor content was associated with the GST activity in primary breast tumors. Colon metastases possessed higher levels of GST activity than primary colon tumors but enzyme activity was independent of the Duke's classification of the tumor. Only tumors of the left colon had levels of GST activity that were higher than those of adjacent normal mucosa. No relationship was evident between either age or sex and the GST activity of any of the tissues examined. GST activity levels may reflect the site-specific ability of tissues to provide cellular protection against xenobiotics.

Biomarkers, Tumor↗

PubMed1991

Aerosolized gamma-interferon and lipopolysaccharide enhances cytotoxicity of murine pulmonary alveolar macrophages.

In vivo stimulation of pulmonary alveolar macrophages (PAMs) may enhance tumor cell cytotoxicity. A model using aerosolized gamma-interferon (gamma-IFN) and lipopolysaccharide (LPS) was developed to induce enhanced PAM activation in vivo in C57BL/6 mice. Mice received four doses of aerosol (2 doses/day) consisting of gamma-IFN (10(4) microU/mouse) and LPS (100 micrograms/mouse). Other groups received either gamma-IFN alone, LPS alone, or saline (control). Cells were harvested by bronchoalveolar lavage. Macrophage cell count demonstrated an increase in macrophage recruitment in the gamma-IFN and LPS group. PAMs were evaluated for in vitro cytotoxicity against B16-F10 melanoma cells. Treatment groups demonstrated enhanced cytotoxicity over controls, and the combination (gamma-IFN plus LPS) was significantly better in cell killing than either treatment modality alone (p less than or equal to 0.02). Activated PAMs selectively killed tumor cells, but did not kill the 3T3 fibroblast cell line. Peritoneal macrophages from mice treated by inhalational gamma-IFN + LPS were enhanced (indicating a systemic effect), but not to the same extent as PAMs. These studies suggest that inhalation of gamma-IFN + LPS can selectively enhance in vivo cytotoxicity of murine PAMs. This may potentially be applicable to human tumor management.

Aerosols↗

PubMed1991

Risk factors for immediate prosthetic postmastectomy reconstruction.

The charts of 44 women who underwent 47 immediate postmastectomy prosthetic breast reconstructions (IPMPBR) with subpectoral prostheses (long-term implant, long-term expandable implant or tissue expanders followed by long-term prosthetic placement) were retrospectively reviewed. Follow-up was from 3 to 49 months (median 18 months). Patient ages ranged from 31 to 77 years (median 42) but 82 per cent were under 60 years old. Indications for mastectomy were infiltrating cancer in 30 patients, intraductal cancer in 11, lobular carcinoma in situ in two and prophylaxis in one. There were 11 patients with pathologic Stage I, 15 with Stage II, three with Stage III and one with Stage IV breast cancer. Adjuvant chemotherapy (CTX) was given to 17 women, adjuvant hormonal treatment to nine, and radiation therapy (RT) to five. One patient had prosthesis extrusion and removal. Two patients had late periprosthetic infections (PPI) with consequent prosthesis removal. CTX did not have a significant association with PPI (two of 14 with CTX vs 0 of 29 without, P = 0.1). However, fill port migrations, prosthesis deflations, and greater than 1 complication were significantly associated with these infections (two of three vs 0 of 38, P = 0.004; two of two vs 0 of 45, P = 0.001; two of four vs 0 of 43, P = 0.006). Skin flap cellulitis and postoperative seroma were also associated with PPI (P less than 0.003 and less than 0.006, respectively). These factors were all also significantly associated with involuntary prosthesis loss (n = 3).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1990

In vitro killing of human malignant mesothelioma by photodynamic therapy.

Photodynamic therapy was investigated as a potential new modality for the treatment of human malignant mesothelioma (HMM) utilizing the H-MESO-1 HMM cell line and the photosensitizing agent, Photofrin-II (PF-II). Up-take of PF-II by H-MESO-1 was documented by incubating H-MESO-1 cells with PF-II and measuring the fluorescence at 625 nm following excitation at 400 nm. Cytotoxicity of photodynamic therapy was determined by incubating H-MESO-1 cells (2 X 10(5)) in microtiter plates for 24 hr with concentrations of PF-II varying from 0 to 10 micrograms/ml. The wells were exposed to gold vapor laser light (628 nm) in doses ranging from 0 to 24,000 J/m2. Twenty-four hours following treatment, [3H]thymidine (1 microCi) was added to each well. Cells were harvested 24 hr later and counted for tritium incorporation. Five replicates were performed for each combination of light and drug. Peak absorption of PF-II by H-MESO-1 was reached within 8 hr. Maximal doses of light alone caused minimal cell killing. PF-II without light was cytotoxic only at the highest concentrations. However, the combination of PF-II at concentrations at or above 2.5 micrograms/ml and light produced a significant increase in cytotoxicity. These data demonstrate that photodynamic therapy can effectively kill human malignant mesothelioma cells in vitro.

Cell Survival↗

PubMed1990

CT-guided needle localization for intraoperative biopsy of the head and neck.

Needle-localized intraoperative biopsy was first described for the nonpalpable breast mass using mammography for needle placement. This technique can be adapted by substituting CT (or MRI) for mammography. It can be a valuable tool in localizing the nonpalpable areas of concern in the head and neck, especially when the location is obscure or the patient has undergone previous radiation and/or surgical therapy.

Biopsy, Needle↗

PubMed1990

Delayed breast abscesses after lumpectomy and radiation therapy.

The incidence of delayed breast abscess as a complication following the treatment of breast cancer has not been reported. A retrospective review of 112 patients (pts) undergoing lumpectomy and radiation therapy (RT) in our institution revealed a six per cent incidence of delayed breast abscess (range 1.5-8 months, median 5 months). Prophylactic antibiotics (P = 1.0), postoperative chemotherapy (P = 1.0), primary vs. re-excisional lumpectomy (P = 1.0), and different surgeons (P = 0.514) were not associated with increased risk of delayed abscess. All abscesses occurred in the first 32 pts of this series. The size of the lumpectomy cavity correlated with the incidence of infection (P = 0.0440). Since six of seven abscess cultures grew staphylococci (coagulase negative three pts, coagulase positive three pts), and four of these pts experienced prior biopsy site infection, skin necrosis or repeated seroma aspirations, a skin source for contamination was suggested. Treatment of the abscesses with antibiotics and immediate drainage produced acceptable but inferior cosmesis. We conclude that a small but significant subset of patients treated with lumpectomy and RT will develop delayed wound infections and that expeditious treatment affords satisfactory cosmesis.

Abscess↗

PubMed1989

Phase I trial of hepatic artery infusion of 5-iodo-2'-deoxyuridine and 5-fluorouracil in patients with advanced hepatic malignancy: biochemically based combination chemotherapy.

Eighteen patients with hepatic metastases primarily from colorectal carcinoma were treated on a phase I protocol employing hepatic artery infusion (HAI) of 5-fluorouracil (FUra) and 5-iodo-2'-deoxyuridine (IdUrd) via implantable infusion pump. Patients received a 14-day continuous HAI of 300 mg/day FUra. During days 8-14 of therapy, patients received IdUrd as a separate 3-h HAI daily x 7. Treatment cycles were repeated every 28 days. IdUrd was escalated from 0.1 to 2.86 mg/kg/day x 7. Myelosuppression and stomatitis were mild and not dose limiting. Hepatotoxicity was dose limiting and similar to that reported for 5-fluoro-2'deoxyuridine alone administered as a 14-day infusion every month. One patient developed a clinical picture consistent with sclerosing cholangitis and another had biopsy-proven cholestasis and triaditis. Catheter complications occurred in 7 of 18 patients. Plasma concentrations of FUra during the 7-day continuous HAI of FUra alone were consistently either undetectable or very low (less than or equal to 0.1 microM). At level 3 (1.0 mg/kg/day IdUrd) and beyond, measurable plasma concentrations of FUra, iodouracil, and IdUrd were found at the end of the daily 3-h infusion of IdUrd. The maximum tolerated dose of IdUrd as administered in this trial is 2.2 mg/kg/day x 7 and the recommended starting dose for further clinical investigation is 1.7 mg/kg/day x 7.

Animals↗

PubMed1989

Recurrent typhlitis. A disease resulting from aggressive chemotherapy.

Neutropenic typhlitis is a frequently fatal disease most commonly reported in leukemics. The authors have treated eight such patients over the last 18 months. All patients had abdominal pain and sepsis during chemotherapy-induced neutropenia. CT scanning was diagnostic in six patients thought to have typhlitis. Two patients were not diagnosed before exploratory laparotomy. The authors have found nonoperative treatment highly effective in patients who do not manifest signs of peritonitis, perforation, gastrointestinal hemorrhage, or clinical deterioration. Recurrent typhlitis was frequent after conservative therapy (recurrence rate, 67 percent), however. One patient underwent an elective right hemicolectomy after a second episode, and typhlitis did not recur despite neutropenia associated with a subsequent course of chemotherapy. It is concluded that successful treatment of this disease hinges on: 1) early diagnosis provided by a high index of suspicion and the use of CT scanning, 2) nonoperative treatment for uncomplicated cases, and 3) elective right hemicolectomy to prevent recurrence.

Adolescent↗

PubMed1989

Resolution of malignant small bowel obstruction after intraperitoneal etoposide therapy.

In the case we have reported, abdominal carcinomatosis with malignant small bowel obstruction (due to metastatic lung adenocarcinoma) developed despite ten cycles of cisplatinvinblastine and eight months of treatment with interferon and interleukin-2. Etoposide (VP-16) administered intraperitoneally as part of a phase I trial produced dramatic relief of the obstruction.

Abdominal Neoplasms↗

PubMed1988

Is percutaneous nephrostomy for hydronephrosis appropriate in patients with advanced cancer?

Twenty patients with advanced pelvic malignancy and secondary hydronephrosis underwent percutaneous nephrostomy between July 1982 and October 1986. Improvement in renal function occurred in 17 patients (85 percent), and survival ranged from 4 days to 2 years. Median survival was 13 weeks, and 55 percent of the patients required multiple hospitalizations for urosepsis. In addition, 55 percent required multiple tube changes. Thirty-five percent of the patients never left the hospital and an additional 35 percent spent less than 6 weeks at home before they died. Median survival for eight patients with primary cancers most frequently associated with carcinomatosis was 7 weeks, and 63 percent of these patients died during hospitalization. The factors of limited survival, significant morbidity, in-hospital mortality, and poor quality of life should be considered before recommending percutaneous nephrostomy in patients with advanced cancer.

Hospitalization↗

PubMed1987

Glutathione S-transferases in human prostate.

A number of human prostatic tissue biopsies have been analyzed for glutathione S-transferase activity, using 1-chloro-2,4-dinitrobenzene (CDNB) as a substrate. Samples from nine patients (age range 61-90) with benign prostatic hypertrophy who had received no prior chemotherapy had a mean glutathione S-transferase activity of 137 +/- 44 nmol/min per mg with a range of 97-237. A qualitative comparison of the glutathione S-transferase of normal prostate and benign prostatic hypertrophy samples was carried out. Approximately 260-fold purification was achieved using glutathione-Sepharose affinity chromatography, with glutathione S-transferase accounting for approximately 0.19-0.33% of the total protein. Substrate specificity determinations suggested similar, but not identical, glutathione S-transferase subunits in normal prostate and benign prostatic hypertrophy. One- and two-dimensional electrophoresis (isoelectric focusing and 12.5% SDS-polyacrylamide gel electrophoresis) identified at least seven stained polypeptides in the purified glutathione S-transferase preparations. These ranged in Mr from approximately 24,000 to 28,500 and in pI from near neutral to basic. Western blot analysis using polyclonal antibodies raised against rat liver glutathione S-transferase suggested crossreactivity with five of the human isoenzymes in both normal prostate and benign prostatic hypertrophy. One of the glutathione S-transferases, present in both normal prostate and benign prostatic hypertrophy, had an Mr of approx. 24,000 and a near-neutral pI and crossreacted immunologically with a polyclonal antibody raised against human placental glutathione S-transferase (Yf, subunit 7 or pi). These data suggest that four glutathione S-transferases are expressed in human prostate, with subunits from each of the major classes alpha, mu and pi. These are characterized as Ya, Yb, Yb' and Yf (analogous alternative nomenclature subunits 1, 3, 4 and 7).

Aged↗

PubMed1987

Cell culture of human colon adenomas and carcinomas.

Cell lines were established from colon adenomas, including tubular and villous polyps, primary adenocarcinomas, and metastases arising in patients with colon adenocarcinomas. The protocol for cultivating these diverse tissues includes primary cultivation of tissue explants on a type I collagen gel followed by nonenzymatic subculture of the epithelial outgrowth. All early passages were accomplished using low subculture ratios. Cultured cells elaborate morphological structures which are similar to features present in the tissues from which they were cultivated. Specifically, all structural features of colon epithelial cells were identified, including junction formation, prominent microvilli, and mucin secretion, in several cell lines. Five cell lines cultured from colonic neoplasms at different stages of cancer progression were selected for detailed characterization. Cells grown from two tubular polyps had normal human karyotypes. Cells from a villous polyp and all adenocarcinomas were aneuploid with stable marker chromosomes. The established cell lines exhibit distinct phenotypes based on growth characteristics in vitro and in athymic mice; and it is suggested that these cell lines represent useful models for studying the evolution of colon cancer from a benign to an aggressive cell type.

Adenocarcinoma↗

PubMed1987

Triple lumen venous access for pediatric bone marrow transplantation candidates.

Multiple routes of vascular access are required in children undergoing bone marrow transplantation to facilitate total parenteral nutrition (TPN); blood withdrawal; and administration of blood products, antibiotics, fluids, and immunosuppressive drugs. Placement of multiple catheters frequently requires multiple venotomies in separate vessels. We have found that both a Broviac catheter and pediatric dual-lumen Raaf catheter can be placed through separate venotomies in the external jugular vein, which provides sufficient routes of vascular access without complications. This technique places only one vessel at risk while minimizing the chance for infection by utilizing two exit sites. We consider this to be the procedure of choice in young patients requiring multiple routes of vascular access.

Bone Marrow Transplantation↗

PubMed1987

Reduced incidence of hepatic metastases by perioperative treatment with recombinant human interleukin-2.

Abdominal operations induce immunosuppression during the time when tumors are manipulated and tumor cells are released into the circulation. The authors tested the hypothesis that the combined effect of these factors may promote the development of metastatic tumor implants and that perioperative treatment with Human Recombinant Interleukin-2 (RIL-2), a known immunostimulant of t, natural killer (NK), and lymphokine activated killer (LAK) cells may reduce the incidence of liver metastases from transplantable rat colon cancers. Hepatic metastases were induced in male Fischer 344 (F344) rats by injecting 10(7) rat colon tumor cells into the portal venous system during laparotomy. Control rats developed tumors by four weeks and were dead by ten weeks. Eleven groups of rats underwent celiotomy with portal vein injection of tumor on day three. Rats received either no RIL-2, RIL-2, or excipient buffer at varying doses on days 1 through 5 or 3 through 7 of these experiments. Animals were assessed for the presence of tumor and the incidence of liver metastases at autopsy (sacrifice and autopsy performed at seven weeks). Eighty-five percent of the rats in the untreated group developed tumor. This compared with only 50 percent of animals receiving 10(3) u/dose (P less than .025) and 42 percent of animals receiving 10(4) u/dose (P less than .01) of Interleukin-2 on days 1 through 5. Animals receiving very high doses of RIL-2 (10(5) or 4 X 10(5) units per dose) had a greater chance of developing tumors than did control rats, or rats receiving lower doses of RIL-2 (P less than .05). It is concluded that the perioperative period may be critical for the implantation and growth of metastatic disease and that perioperative immunostimulation with RIL-2 can decrease the incidence of tumors in these animals. This model may have relevance to the treatment of human colon cancer.

Animals↗