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Biomedical subjects

M S Granick

Publications and source records attributed to M S Granick.

At least 37 records · Page 2Linked to original sources
PubMed1996

Modulation of cranial bone healing with a heparin-like dextran derivative.

Substituted dextran polymers have been shown to bind growth factors and protect them from enzymatic degradation. Using this information, other researchers have been able to use these substituted dextrans to enhance the healing of bone in an environment where bone would otherwise not regenerate. We used substituted dextran polymers to evaluate their ability to accelerate the healing of cranial bone in a rabbit model. We were able to document a more rapid rate of healing and demonstrate micrographic evidence to support that conclusion. Possible mechanisms are postulated.

Analysis of Variance↗
PubMed1995

Thrombospondin and transforming growth factor-beta 1 increase expression of urokinase-type plasminogen activator and plasminogen activator inhibitor-1 in human MDA-MB-231 breast cancer cells.

BACKGROUND: Thrombospondin is a high molecular weight adhesive glycoprotein that has been shown to function in mechanisms of tumor progression. The authors' previous studies have shown that thrombospondin promotes human lung carcinoma invasion by up-regulation of the plasminogen activator system through a mechanism involving the activation of transforming growth factor-beta 1 (TGF-beta 1). In this study, a similar thrombospondin-mediated mechanism operative in breast carcinoma cells is described. METHODS: The effect of thrombospondin and TGF-beta 1 on the capacity of a line of breast carcinoma cells to activate plasminogen was measured as well as the physiologic consequences of these activities on cell adhesion and proliferation. Plasminogen activation was assessed by measuring the plasmin activity and plasminogen activator inhibitor-1 (PAI-1) levels in cell-conditioned media and the cell-associated urokinase-type plasminogen activator (uPA) levels. RESULTS: Treatment of MDA-MB-231 breast carcinoma cells with either thrombospondin or TGF-beta 1 caused increased secretion of PAI-1 with a concomitant decrease in plasmin activity, whereas cell-associated uPA expression was increased with respect to controls. Thrombospondin (40 micrograms/ml) or TGF-beta 1 (5 ng/ml) stimulated the cells to secrete 5.5- and 6.7-fold more PAI-1 than controls, respectively, and caused decreased plasmin activity in the cell culture medium. Conversely, either thrombospondin (40 micrograms/ml) or TGF-beta 1 (5 ng/ml) caused the cells to express 4.55- and 5.38-fold more uPA than controls, respectively. Thrombospondin and TGF-beta 1 induced a more flattened and spread appearance in the cells with no effect on proliferation. These effects could be reversed with antibodies to either thrombospondin or TGF-beta 1 and were not due to contamination of thrombospondin with active TGF-beta 1. CONCLUSIONS: Thrombospondin and TGF-beta 1 function similarly to increase cell-associated uPA and cell-secreted PAI-1. These data suggest that thrombospondin may not only function as an adhesive molecule, but through a mechanism involving the activation of TGF-beta 1, may modulate cell surface protease expression. In addition, these observations suggest that thrombospondin and TGF-beta 1 could promote metastasis by increasing uPA-mediated cell invasion, whereas through the action of PAI-1, also protect blood-born tumor emboli from destruction by host fibrinolytic enzymes.

Breast Neoplasms↗
PubMed1995

The effect of thrombospondin on oral squamous carcinoma cell invasion of collagen.

BACKGROUND: Thrombospondin (TSP), a cell matrix protein, and transforming growth factor beta (TGF-beta), a growth regulatory protein, play roles in tumor progression. The purpose of this study was to investigate the effects of TSP and TGF-beta on tumor cell invasion. MATERIALS AND METHODS: Tumor cell invasion assays were performed using a modified Boyden chamber apparatus with collagen-coated membranes. The KB oral carcinoma cell line was studied in serum-free media. Invasion was measured as the summation of the number of cells in five representative low-power fields (x 100) traversing the collagen barrier after a 3-hour incubation period. The effects of antibodies against TSP, TGF-beta and the cysteine-serine-valine-threonine-cysteine-glycine (CSVTCG)-specific TSP receptor were also evaluated. RESULTS: TSP caused a dose-dependent stimulation of tumor cell invasion. Antibodies against TSP, its CSVTCG-specific receptor, and TGF-beta inhibited TSP-promoted invasion by 50% to 71%. CONCLUSIONS: TSP and its CSVTCG-specific receptor promote KB cell invasion of collagen through the production and/or activation of TGF-beta.

Amino Acid Sequence↗
PubMed1994

Thrombospondin (TSP) and transforming growth factor beta 1 (TGF-beta) promote human A549 lung carcinoma cell plasminogen activator inhibitor type 1 (PAI-1) production and stimulate tumor cell attachment in vitro.

A growing body of evidence has recently implicated TSP and TGF-beta in the process of malignancy, such as tumor cell proliferation, tumor angiogenesis, and metastasis. The purpose of the present study was to evaluate potential mechanisms of TSP and TGF-beta in tumor cell attachment and invasion. Our results indicate that both TSP and TGF-beta promoted tumor cell attachment and spreading in the presence of plasminogen. The mechanism for these effects appeared to be due, in part, to the capacity of TSP and TGF-beta to induce tumor cell production of (PAI-1). PAI-1, which is a natural inhibitor of tumor-cell associated urokinase-type plasminogen activator (uPA) activity, inhibited activation of plasminogen to plasmin in the growth media, thereby preventing plasmin-induced detachment of cells. The TSP-promoted production of PAI-1 could be inhibited not only by anti-TSP antibodies but also by a neutralizing antibody against TGF-beta. These results suggest that TSP by a mechanism involving TGF-beta can promote cell adhesion through stimulation of tumor cell secretion of PAI-1. These data provide evidence that TSP not only has the capacity of functioning as a matrix protein to directly promote cell-substratum adhesion but that TSP can also stimulate cell adhesion and spreading by modulating cell surface protease expression through stimulation of tumor-associated production of PAI-1.

Adenocarcinoma↗
PubMed1994

Computer-assisted image analysis of tumor sections for a new thrombospondin receptor.

BACKGROUND: A cell surface receptor (50 kd) has been recently identified in malignant cells that recognizes the tumor cell adhesive domain (ie, cysteine-serine-valine-threonine-cysteine-glycine [CSVTCG]) of thrombospondin (TSP). This CSVTCG-specific TSP receptor can be considered as a new tumor marker, and its concentration on the cell surface may correlate directly with the capacity of tumor cells to invade and metastasize. MATERIALS AND METHODS: Six patients with primary, stages III and IV squamous cell carcinomas of the head and neck were studied. Tumor sections were specifically stained for this receptor with immunohistochemical techniques. The stained specimens were then subjected to computer-assisted image analysis. The area of positive staining and the heterogeneity of the pattern of staining were compared to peritumoral angiogenesis and clinical outcome of the patients. RESULTS: The results indicate that those patients with a high and homogenous positive stain score (mean +/- standard error [SE] 78 +/- 5%) for the CSVTCG-specific TSP receptor had high microvessel density and died from metastatic disease within 12 months of initial treatment (correlation coefficients = 0.95 and 1, respectively). Patients with a low and heterogenous positive stain score for receptor (mean +/- SE 8 +/- 2%; P < 0.001) had low microvessel counts and remained disease-free for at least 2 years. There was no relationship between receptor density and histologic classification of the primary tumors. CONCLUSION: The CSVTCG-specific TSP receptor, quantified through image analysis of immunohistochemical stained tissue sections, is highly predictive of clinical outcome in patients with squamous cell carcinomas of the head and neck.

Adult↗
PubMed1994

The relationship of angiogenesis to biological activity in human squamous cell carcinomas of the head and neck.

Tumor angiogenesis has recently been related to tumor growth and metastasis, which determine the clinical outcome of the patient. This study was designed to determine the relationship between angiogenesis in primary squamous cell carcinomas (SCC) of the head and neck and the development of recurrent or metastatic disease, or both. Different SCC of the head and neck were studied. Microvessels were selectively stained using a monoclonal antibody for factor VIII. Microvessel counts were performed in the tumor, in the tissues immediately adjacent, and in normal tissues of similar topographies. Microvessel counts were then correlated with clinical outcome (development of recurrent or metastatic disease, or both). Recurrent or metastatic disease, or both, developed in patients with high microvessel counts (mean, 121.25) in the tissues adjacent to the tumor 7 to 16 months after initial treatment. Those with low microvessel counts (mean, 33.75) were disease-free for 16 months to 6 years (p < 0.01). Microvessel counts inside the tumor were also higher in those in whom recurrences or metastasis, or both, developed, but were not statistically significant. In this study, angiogenesis was directly related to clinical outcome. Thus, angiogenesis may be an independent predictor of recurrent or metastatic disease, or both, which could help in the selection of patients with SCC of the head and neck for aggressive therapy.

Carcinoma, Squamous Cell↗
PubMed1994

Management of infected laminectomy wounds.

Wound infection after lumbar, thoracic, or cervical laminectomies is a rare but potentially devastating complication. It can range in severity from superficial wound infection to an extensive wound dehiscence. The usual treatment of these wounds consists of intensive local care, debridement, and appropriate antibiotic therapy. Secondary healing can result in chronic, painful wounds that are difficult to manage and can create the potential for osteomyelitis. Seven cases of infected dehiscent laminectomy wounds are presented. Either critical structures were exposed, or the patients did not heal after secondary or delayed primary closures. In each case, full healing was attained by means of reconstruction with a regional muscle flap. We propose that muscle flap reconstruction offers an excellent alternative for the reconstruction of difficult postlaminectomy wounds.

Adult↗
PubMed1994

Wound care in the elderly patient.

Wound care in the elderly population requires careful attention to the medical status of the patient. The patient's underlying medical condition can often dictate what reconstructive options are appropriate. Many reconstructive techniques are available to repair a wide variety of wounds.

Aged↗
PubMed1993

The cross-leg flap revisited.

Although free flaps are currently the gold standard for distal lower extremity reconstruction, situations occasionally arise when alternative methods are needed. We present three cases of cross-leg flaps, which have been modernized with current external fixation technology and current understanding of vascular anatomy. All cross-leg flaps were based on the axial blood supply of the posterior descending subfascial cutaneous branch of the popliteal artery. This axial flap afforded considerable length and well-vascularized tissue. All patients were placed in external fixation devices. Adjacent lower extremity joints were exercised during the period of attachment. There were no major complications or flap failures. All patients were ambulatory postoperatively. We conclude that the cross-leg flap, using external fixation techniques and axially based flaps, can be successfully and expeditiously used to cover defects of the lower extremities.

Adult↗
PubMed1993

Reconstruction of radiation-induced chest wall lesions.

Radiation-related ulcers of the chest wall provide a great challenge to reconstructive surgeons because of the necessity of protecting the underlying vital structures and the difficulty in repairing irradiated tissues. To evaluate the efficacy of treatment, 24 patients who underwent reconstruction of radiation related ulcers of the chest wall were retrospectively reviewed. A variety of muscle and musculocutaneous flaps as well as omentum and microvascular tissue transfers were used to reconstruct these defects. The defects in the chest wall arose from spontaneous breakdown of irradiated tissue, tumor recurrence, or nonhealing after surgical procedures performed in the irradiated field. Our treatment protocol consisted of aggressive debridement of all affected tissues including skeletal tissues when necessary. The application of a tension free closure using a flap was then performed. Skeletal support was provided in three reconstructions. There were no mortalities, the morbidity rate was 29% (six minor, one major complication), and the mean hospital stay was 10.9 days. None of the patients required prolonged ventilator support. In all but 2 patients, who were left with small chronic granulating nonhealing wounds, complete wound healing was achieved. We conclude that chest wall reconstruction of radiation-related ulcers can be achieved with minimal morbidity in an acceptable period of inpatient hospital care using a variety of vascularized tissue transfers.

Aged↗
PubMed1993

Radiation-related wounds of the chest wall.

Irradiation-associated chest wall lesions pose a significant health hazard to the patient. The principles of management include (1) biopsy of any open wounds to rule out the recurrence or persistence of tumor, (2) aggressive debridement of all offending tissues, and (3) reconstruction with well-vascularized flap tissue. Numerous questions arise regarding the practical management of these patients. The controversies that have arisen during our management of more than 100 of these patients have been discussed. It is appropriate to perform reconstruction following nonhealing of a superficial ulcer or immediately following the excision of a full-thickness chest wall defect. Hyperbaric oxygen can serve as a useful adjunct. It is rarely necessary to use a prosthetic material for the purpose of chest wall stabilization during the reconstruction of full-thickness defects. Paradoxic chest wall movement in the postoperative period does not significantly affect pulmonary function tests and is generally a transient problem. Subtotal excisions are frequently necessary. As long as all of the necrotic or tumor-bearing tissue has been fully removed, these wounds can be expected to heal in most instances by placing vascularized tissue into the defect. Operative sites in previously irradiated chest wall tissue can be expected to heal if proper and careful surgical technique is employed. Nevertheless, there is a risk of wound breakdown following any surgery in irradiated tissue. Finally, we believe it is appropriate to proceed with aesthetic recontouring of chest wall deformities associated with irradiation exposure.

Adult↗
PubMed1993

Management of radiation-associated pelvic wounds.

Radiation-associated pelvic wounds should be managed by complete excision of all affected tissues and reconstruction with a vascularized flap. The complex anatomy and function of the perineum and pelvis create a variety of reconstructive demands. This article attempts to demonstrate the diversity of the problems that can occur in this region as well as to describe the varied options for reconstruction.

Female↗
PubMed1992

Posttraumatic upper extremity wound coverage utilizing the extended deep inferior epigastric flap.

The extended deep inferior epigastric artery (DIEA) flap was used in 4 patients with traumatic mid upper extremity wounds. Although there are numerous flaps available for resurfacing upper extremity defects, including the groin, thoracoepigastric, and a host of microvascular flaps, in each of these patients a preoperative consideration necessitated a novel approach. The DIEA flap is based on an axial vascular watershed resulting in a long, thin, well-vascularized, supple skin flap, which proved extremely effective in solving the reconstructive needs of these patients. The flap is technically simple to elevate and quite versatile. In all patients, the flaps survived and healing of the wounds was achieved. The DIEA flap should be considered a valuable reconstructive alternative when faced with elbow and forearm defects.

Abdominal Muscles↗
PubMed1992

Pencil-core granuloma.

Noncaseating granulomas present as a delayed foreign-body reaction to retained pencil-core fragments. The clinical appearance of the lesion can closely resemble melanoma. Surgeons who use pencils as surgical marking implements should be aware that there is a potential risk of developing late pencil-core granulomas. This risk can be reduced by carefully removing any pieces of pencil lead from the wound.

Adult↗