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Biomedical subjects

J L Frank

Publications and source records attributed to J L Frank.

At least 19 recordsLinked to original sources
PubMed2000

Routine chest roentgenography is unnecessary in the work-up of stage I and II breast cancer.

PURPOSE: Clinical practice guidelines of many professional societies call for routine staging chest x-rays (SCXR) for all patients with invasive cancer. Given the estimated 157,000 patients annually for whom this recommendation pertains, this screening examination represents a considerable health care expenditure. If it were shown that SCXR rarely changed the management of low-risk subsets of this population, it might be possible to selectively omit this practice from the care of these patients with substantial resultant cost savings. PATIENTS AND METHODS: All patients with clinical stage I and II breast cancer presenting to the Baystate Medical Center from 1989 through 1997 were identified through the Tumor Registry. Their hospital records were reviewed for clinical presentation and documentation of SCXR. RESULTS: One thousand four hundred ninety-four patients were identified with clinical stage I and II disease. SCXR were available for review on 1,003 patients. Only one asymptomatic patient was upstaged to stage IV based on a SCXR. Two patients with primary lung tumors were also identified. These data demonstrate an asymptomatic pulmonary metastasis detection rate of 0. 099% (95% confidence interval, 0.0% to 0.6%). The total charges of SCXR for this group approached $180,000. CONCLUSION: These data demonstrate the low diagnostic yield and high cost of routine SCXR in the management of asymptomatic patients with clinical stage I and stage II breast cancer. Because other studies have shown that SCXR changes neither quality of life nor overall survival, SCXR should be limited to symptomatic patients in whom metastatic disease is suspected.

Breast Neoplasms↗
PubMed2000

Multiple ejaculations and chronic fluoxetine: effects on male rat copulatory behavior.

Male rats were treated with fluoxetine (FLX) or vehicle daily for 14 days and copulatory behavior tested on day 15. Rats were either mated to three ejaculations or to sexual exhaustion. Both standard measures and the mount bout analysis were used to evaluate the effects of the chronic FLX on male rat copulatory behavior. Only 56.25% of the animals treated with FLX achieved three ejaculations. FLX inhibited the consumatory aspect of male sexual behavior, especially the ability to achieve three ejaculations, but there was no effect on the propensity of the male to pursue the female. These differences were observed for the first three ejaculations. Analysis of the last three ejaculations in those animals that mated to exhaustion did not reveal an effect of FLX. The behavioral pattern of FLX-treated animals during the first three ejaculations resembled that observed during the last three ejaculatory series in the vehicle-treated animals that mated to exhaustion. The results are discussed in terms of the serotonergic effects on male rat sexual behavior.

Animals↗
PubMed2000

The effects of St. John's Wort (Hypericum perforatum) on NK cell activity in vitro.

St. John's Wort (Hypericum perforatum; H. perforatum) is a popular herbal supplement used to treat mild to moderate depression. H. perforatum possesses serotonergic properties such as inhibition of serotonin (5-hydroxytryptamine; 5-HT) reuptake. Serotonergic pharmacotherapy is associated with amelioration of depression as well as increases in natural killer (NK) cell activity (NKCA). Also, 5-HT and 5-HT analogs augment NKCA in vitro. Considering the serotonergic properties of H. perforatum, the effects of H. perforatum on NKCA were assessed in vitro. Mononuclear cells (MNCs) from normal donors were exposed in vitro to an extract of H. perforatum (LI160s) or established 5-HT stimulators of NKCA. After an overnight incubation, cells were washed and a standard 51Cr-release cytotoxicity assay performed to assess NKCA. LI160s at all concentrations failed to augment NKCA. However, in corroboration of previous studies, 5-HT, the selective serotonin reuptake inhibitors (SSRIs), paroxetine and norfluoxetine, and alpha-interferon augmented NKCA above control levels. Though an efficacious treatment for mild to moderate depression, H. perforatum differs from commonly prescribed serotonergic antidepressants insofar as H. perforatum fails to enhance NKCA in vitro. Therefore, the present results are consistent with pharmacologic studies indicating that H. perforatum possesses, at best, weak serotonergic activity.

Adult↗
PubMed1999

The unsatisfactory margin in breast cancer surgery.

BACKGROUND: Surgical margin involvement with breast cancer usually results in obligatory reexcision or mastectomy. While unalterable occult host and pathologic factors may interfere with margin clearance during the initial excision, it is possible that alterations in surgical technique might increase the likelihood of obtaining satisfactory margins. METHODS: Two hundred and thirty-five patients who were candidates for breast conservation therapy were identified for 1991 and 1996 using the Tumor Registry. Margins were defined as "unsatisfactory" if there was microscopic involvement with tumor or the margin was close at initial excisional biopsy and the surgeon opted for reexcision. Multiple logistic regression analyses of factors associated with margin status were performed. RESULTS: One hundred thirty-two (56%) patients had positive or close (unsatisfactory) margins; this rate increased from 51% in 1991 to 59% in 1996. Patients with unsatisfactory margins underwent more procedures (mean 2.0 versus 1.2; P <0.0001) than patients whose margins were satisfactory. The breast conservation rate for patients with unsatisfactory margins was 64% compared with 99% for patients with satisfactory margins. A multiple logistic regression demonstrated that patients with unsatisfactory margins were 67 times more likely to have a mastectomy than patients whose margins were satisfactory after adjusting for other significant factors (P <0.0001). The practice of fine needle aspiration biopsy, orientation of specimen margins by the surgeon, and reexcision of tumor at the first operation were statistically significant technical factors in obtaining satisfactory margins. Significant pathology factors were extensive intraductal component (EIC), lobular or ductal extension, and tumor size. CONCLUSION: These data show that technical factors in the surgical management of breast cancer, as well as biological factors such as EIC, can influence the success of breast conservation.

Biopsy↗
PubMed1998

Hemobilia complicating hepatic cryosurgery.

We describe a 58-year-old man who developed hemobilia following hepatic cryotherapy. This was complicated by acute pancreatitis and recurrent cholangitis, which necessitated multiple endoscopic procedures (including biliary stenting) for successful management. As cryotherapy becomes more widely applied in the management of patients with liver tumors, it is essential that surgeons safeguard against the development of arteriobilious fistulae.

Acute Disease↗
PubMed1994

p53 tumor suppressor oncogene expression in squamous cell carcinoma of the hypopharynx.

BACKGROUND: Although abnormalities of the p53 tumor suppressor oncogene system are being detected in many human cancers, the frequency and prognostic significance of such events in squamous cell cancer of the head and neck remain unknown. METHODS: Immunohistochemical studies were performed on archival tumor tissue taken from 43 patients with squamous cell carcinoma of the hypopharynx. Statistical analyses examining potential associations between p53 oncoprotein accumulation and various clinicopathologic parameters (including survival) were conducted. RESULTS: Sixteen (37%) tumors demonstrated strong specific staining for p53. Patients whose tumors stained strongly for p53 were significantly younger, presented at a more advanced clinical disease stage, and tended to have increased expression of epidermal growth factor receptor (P = 0.056). There was no correlation between p53 expression and the incidence of multiple primary cancers, tumor grade, DNA ploidy, or percent of S-phase. Median survival times were 11.6 months and 18.0 months for the p53-positive and p53-negative groups (NS). A Cox regression analysis confirmed the lack of significance of p53 in overall survival. CONCLUSIONS: These data suggest that although abnormalities of the p53 oncoprotein are common in this cancer, this finding is of little clinical significance.

Age Factors↗
PubMed1994

Nd:YAG laser excision of a giant gingival pyogenic granuloma of pregnancy.

A 19-year-old Hispanic nullipara experienced the rapid growth of an oral lesion on the right lower gingiva which she had first noticed at 29 weeks gestation. The lesion interfered with oral hygiene and eating. At surgery, the lesion measured 3.5 x 2.5 x 2.0 cm. Biopsy confirmed a pyogenic granuloma ("granuloma gravidarum"). Panorex films showed no bony invasion. The lesion was excised using the Nd:YAG laser under general anesthesia when the patient had reached 36 3/7 weeks gestation. We chose the Nd:YAG laser over the CO2 laser for the removal of this very vascular lesion, because of its superior coagulation characteristics. This technique results in removal of the lesion with less danger of bleeding than with any other surgical technique. The patient did well postoperatively, delivered a healthy 3,884 g infant at 40 6/7 weeks gestation, and has had no recurrence after 15 months of follow-up.

Adult↗
PubMed1994

Postoperative radiotherapy improves survival in squamous cell carcinoma of the hypopharynx.

BACKGROUND: Postoperative radiation is considered to be "standard of care" therapy for advanced, resectable squamous cell carcinoma of the head and neck. This approach has been supported by retrospective data but has not been validated in randomized clinical trials. PATIENTS AND METHODS: The present analysis examined the clinical course of 110 patients with squamous cell cancer of the hypopharynx treated with surgery alone (n = 65) and postoperative radiotherapy alone (n = 45) between 1966 and 1990. Staging of patients was performed using the 1988 American Joint Committee on Cancer criteria. Cox regression analyses identified clinical and pathologic factors that were significant for disease-free and overall survival. Crude and adjusted cancer-specific survival rates were calculated. RESULTS: The postoperative radiotherapy group presented with more advanced disease than the surgery alone group (stage III and IV combined, 96% versus 77%, P = 0.015). Crude 5-year cancer-specific survival probabilities were 43% for the postoperative therapy group and 27% for the surgery alone group (P = NS). Adjusted 5-year survival rates, correcting for differences in significant prognostic variables between groups, were 18% and 48%, respectively, for the surgery and postoperative radiotherapy groups (P = 0.029). CONCLUSIONS: The addition of postoperative radiotherapy was associated with improved disease-free and adjusted overall cancer-specific survival in patients with advanced hypopharyngeal squamous cancer. The potential survival benefit of postoperative radiotherapy should be addressed in a randomized clinical trial.

Carcinoma, Squamous Cell↗
PubMed1993

Epidermal growth factor receptor expression in squamous cell carcinoma of the hypopharynx.

Expression of the epidermal growth factor receptor (EGFR) has been demonstrated in normal and malignant squamous epithelia. Its presence has been suggested to be important in the pathophysiology and prognosis of epithelial cancers. Archival tumour specimens from 57 patients with squamous cell carcinoma of the hypopharynx were studied using OM-11-951, a new murine anti-EGFR monoclonal antibody which recognizes the receptor on deparaffinized tissue. By visual inspection, 28 (49%) tumours were EGFR negative; 29 (51%) tumours were EGFR positive. While patients whose tumours were EGFR positive were younger, there was no significant correlation with other clinical or pathological variables (including grade and stage). Patients whose tumours were EGFR negative had a median survival of 21 (95% CI 4.3-37.7) months compared with a median survival of 17 (95% CI 11.4-22) months for patients whose tumours were EGFR positive. The difference was not statistically significant. A multiple regression analysis did not demonstrate EGFR status to be important in predicting survival. These data cast doubt on the prognostic significance of EGFR expression in this neoplasm.

Antibodies, Monoclonal↗
PubMed1993

Expansion and tumour specific cytokine secretion of bryostatin-activated T-cells from cryopreserved axillary lymph nodes of breast cancer patients.

Current adoptive immunotherapy strategies in cancer patients require large numbers of activated T-cells and are limited by the availability of autologous tumour. We describe a novel method of T-cell activation that produced relatively rapid, high-fold expansion of stored, frozen lymphocytes obtained from the lymph nodes of 20 breast cancer patients during axillary dissection but does not require autologous tumour. In vitro exposure of thawed cells to bryostatin-1 (B), a non-tumour promoting protein kinase C activator and ionomycin (I), a calcium ionophore, at day 0 followed by culture in low dose interleukin-2 (IL-2 20 units ml-1) and restimulation again on day 10 results in 269-28,206 fold (geometric mean = 2254) expansion in cell numbers counted 17 days after initial stimulation. Analysis of cell surface markers revealed that B/I expanded human cells were predominantly T-cells (83-97%) and consisted of a mixture of CD8+ (46-74%) and CD4+ (4-30%) cells. B/I expanded cells did not lyse autologous tumour cells when tested in a 4-h 51Cr release assay, but murine studies reported previously have demonstrated specific and curative in vivo efficacy in MCA-105 tumour-bearing mice despite an inability to lyse autologous tumour in vitro. B/I expanded T-cells from five of six patients secreted the cytokines tumour necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) in response to co-culture with autologous tumour cells but not with irrelevant tumour. These results are analogous to findings in a murine model, in which non-cytolytic B/I expanded T-cells mediated specific, curative anti-tumour effects in vivo, and lay the groundwork for a clinical trial of this novel strategy for the adoptive immunotherapy of breast cancer patients.

Adjuvants, Immunologic↗
PubMed1992

Modulation of cell cycle kinetics in human cancer with total parenteral nutrition.

Prior DNA flow cytometric data from the laboratory of the Division of Surgical Oncology, Massey Cancer Center, demonstrated an increase in the hyperdiploid compartment of tumor cells taken from patients with squamous cell carcinoma of the head and neck after a course of total parenteral nutrition (TPN). To assess a putative increase in the percentage of tumor cells actively synthesizing DNA in this system, the authors administered bromodeoxyuridine (BrdU) intravenously to ten patients before and after the administration of TPN. Cell suspensions prepared from biopsy specimens of normal oral mucosa and tumor tissue were analyzed with flow cytometric study. Before TPN administration, the mean percentage of tumor cells incorporating BrdU was 2.47 +/- 1.11%. After TPN administration, the percentage of S-phase cells increased significantly (P less than 0.05) to a mean of 4.52 +/- 2.67%. Before TPN was given, normal mucosa demonstrated a mean of 7.97 +/- 2.69% of cells incorporating BrdU. After TPN was given, a mean of 8.47 +/- 2.51% was seen (not significant [NS]). A potential strategy for the use of TPN to enhance tumor cell susceptibility to S-phase-specific chemotherapy is strongly suggested by these data.

Adult↗
PubMed1992

Stage III breast cancer: is neoadjuvant chemotherapy always necessary?

Optimal management of locally advanced breast cancer is controversial. Claims of superiority for neoadjuvant systemic therapy are based on comparisons with outdated historical control groups who received no chemotherapy. Between 1978 and 1987, 118 patients with locally advanced breast cancer underwent treatment and follow-up at the Medical College of Virginia. Median follow-up was 44 months (range 3-119 months). Actuarial 5-year survival for the entire group was 54%. This compares favorably with recent series using neoadjuvant chemotherapy in which 5-year survival rates of 40-65% have been reported. Primary tumor size larger than 9 cm, metastases to more than 50% of regional lymph nodes, and the presence of inflammatory disease were significant prognostic indicators. This series represents a contemporary control group of patients with locally advanced breast cancer in whom conventionally accepted guidelines for local and postoperative systemic adjuvant therapy were used. Until the optimal sequence of therapy is determined by prospective randomized trials, series such as this may serve as more appropriate controls to which the results of new therapies could be compared.

Adenocarcinoma↗
PubMed1992

Enhancement of cytotoxic T lymphocyte growth from spleens of P815-tumor-bearing host mice with mafosfamide.

Mafosfamide (Mafo) is an analog of cyclophosphamide that does not require hepatic activation and therefore has in vitro activity. The present study was conducted to determine the effects of in vitro treatment with Mafo on the generation and growth of cytotoxic T lymphocytes (CTL) from tumor-bearing host mice (TBH). In contrast to early (day-11) TBH splenocytes, splenocytes from late (days 18-20) P815 TBH mice suppress the in vitro generation of CTL. Treatment of late TBH splenocytes in vitro with 5-15 microM Mafo resulted in a reduced ability of these cells to suppress in vitro CTL generation. Treatment of late TBH splenocytes with 10 microM Mafo also inhibited their ability to suppress adoptive immunotherapy of intradermal tumors with immune splenocytes. These doses of Mafo were selectively toxic to the suppressive effects of late TBH splenocytes, since treatment of early TBH splenocytes with 1-10 microM Mafo did not significantly inhibit CTL generation. Spleen cells from early (days 10-12) TBH mice, carried in long-term in vitro sensitization cultures in the presence of tumor cells and 20 U/ml human recombinant interleukin-2, did not increase in cell number over time. However, when pretreated with 3 microM Mafo, this population of tumor-sensitized lymphocytes demonstrated 450-fold growth over 6 weeks as compared to the static cell numbers for the untreated controls. High levels of tumor-specific cytolytic activity were maintained in these expanded cells. These results suggest that Mafo pretreatment markedly and selectively inhibits suppressor cells that limit long-term expansion of splenic CTL in culture and inhibit adoptive immunotherapy of solid tumors.

Acrolein↗
PubMed1992

Bryostatin 1 activates T cells that have antitumor activity.

Several strategies have been used to stimulate the growth of tumor-specific T cells in place of tumor antigen. One approach is to use pharmacologic agents to activate the second messenger pathways of T-cell activation. In the present study, we examined the ability of the protein kinase C activator bryostatin 1 (B) plus the calcium ionophore ionomycin (I) to stimulate the growth of lymphocytes obtained from the axillary lymph nodes (DLN) draining a progressively growing intradermal plasmacytoma tumor. Draining lymph node cells were initially cultured with autologous tumor cells and 20 U/ml of interleukin-2 (IL-2) for 7 days. The lymphocytes were then incubated with various concentrations of bryostatin 1 plus 1 microM ionomycin and cultured for an additional 14 days in IL-2. DLN cells initially cultured with autologous tumor and then restimulated with 5 nM bryostatin 1 and 1 microM ionomycin exhibited marked in vitro proliferation and 15-fold expansion of cell numbers over 2 weeks. The cells expanded with B/I were predominantly CD8+ T cells and retained specific in vitro cytotoxicity against autologous tumor. When adoptively transferred to mice with established liver metastases, DLN cells restimulated with B/I-mediated specific tumor regression.

Animals↗
PubMed1991

A cytotoxic T-lymphocyte clone derived from mice with progressively growing tumors.

Tumor-specific T-cell clones were derived from spleen cells of mice bearing a syngeneic PHS-5 tumor (a P815 mastocytoma mutant). Cells were expanded in vitro and characterized and assayed for activity against the relevant tumor in vivo. Clone cells were CD4-, CD8+ T lymphocytes, as determined by fluorescence activated cell sorting analysis and were specifically cytotoxic against P815 tumor cells in vitro, as shown in chromium 51 release assays. These cells require both antigen and interleukin 2 to proliferate; neither alone is sufficient, even with the addition of interleukin 1. In an experimental P815 liver metastasis model, the adoptive transfer of GD11 or GD11.17 clone cells and injection of recombinant interleukin 2 (7500 U intraperitoneally) 3 days after infusion of tumor cells reduced the number of tumor nodules, while the adoptive transfer of lymphokine-activated killer cells was ineffective.

Animals↗