Search PubMed⌕ Search

Biomedical subjects

M I Ross

Publications and source records attributed to M I Ross.

107 records · Page 6Linked to original sources
PubMed1991

Study of tumor-infiltrating lymphocytes for adoptive therapy of renal cell carcinoma (RCC) and metastatic melanoma: sequential proliferation of cytotoxic natural killer and noncytotoxic T cells in RCC.

We investigated the immunological properties of interleukin-2 (IL-2)-activated tumor-infiltrating lymphocytes (TIL), which were used for adoptive therapy of renal cell carcinoma (RCC) (seven patients) by focusing on natural killer (NK) cells, and metastatic melanoma (six patients) by focusing on cytotoxic T lymphocytes. TIL from five of seven cases proliferated well in culture with AIM-V serum-free medium and 1000 U/ml rIL-2 in 3-L gas permeable bags, whereas TIL from two RCCs exhibited delayed proliferation. Proliferation of CD3-CD56+ NK cells with major histocompatibility complex-nonrestricted cytotoxicity in RCC-TIL (n = 6, mean = 651-fold, ranging from 39- to 3450-fold) for the first 2-4 weeks was 63 times higher than that of noncytotoxic CD3+ T cells (n = 6, 10.3-fold ranging from 0.8 to 35-fold). Thereafter, CD3+ T cells predominantly proliferated, and proliferation of CD3+ T cells (n = 5, 743-fold) for 5-6 weeks were 24 times higher than that of CD3-CD56+ NK cells (n = 5, 31-fold). Significant numbers of RCC-TIL became adherent to the surfaces of the bags several weeks after initiation of culture. These adherent TIL consisted of more CD3-CD56+ NK cells and exhibited higher cytotoxicity than did nonadherent TIL. Adherent RCC-TIL produced interferon (IFN)-gamma, while nonadherent TIL did not. These results suggest that initially cytotoxic CD3-CD56+ NK cells and, later, noncytotoxic CD3+ T cells proliferated in culture of RCC-TIL for adoptive therapy. These noncytotoxic TIL were primarily transferred to RCC patients, who also received cyclophosphamide, IL-2, and IFN-alpha. In contrast to RCC-TIL, IL-2-activated melanoma TIL consisting of all CD3+ T cells displayed modest levels of cytotoxicity, primarily restricted to autologous melanoma cells in all cases tested. The cytotoxic melanoma TIL were adoptively transferred to melanoma patients. Three of seven RCC patients responded to the adoptive therapy.

Carcinoma, Renal Cell↗
PubMed1991

The current management of cutaneous melanoma.

Theoretically ELND may be beneficial for the subset of patients who are likely to have occult metastases at the time of diagnosis. The natural history of melanoma, well described from large data bases, has identified a group of patients with "intermediate-thickness" melanomas as the potential beneficiaries. However, pathologic specimens obtained from ELND have demonstrated a much lower incidence of occult disease (15%) than what would be anticipated based on the estimated risk of developing clinically detectable metastasis, more than 50%. Possible explanations for this discrepancy are as follows: (1) routine pathologic examination fails to detect micrometastases accurately thus, grossly underestimating the true incidence of occult disease and/or (2) patients who are at high risk for metastases have not yet developed regional disease at the time of diagnosis and performance of the ELND. In the latter situation, ELND would provide expectant palliation by preventing regional node relapse but would not be expected to impact on survival. Clearly, however, at least three retrospective studies have demonstrated a survival benefit when using ELND for the treatment of patients in the subgroup with intermediate-thickness melanomas. Prospective studies have not confirmed these same results, but they have not targeted the study to the same group of patients. In order to resolve the differences, we have initiated a prospective randomized multi-institutional surgical trial to ascertain the efficacy of ELND in patients with tumor thickness between 1 and 4 mm. More than 700 patients have been entered on this study. Results should provide valuable insights as to the true incidence of occult regional disease and determine if the removal of this disease translates into a survival benefit. In the meantime, the practice of ELND should be a selective one. The decision should be individualized in an attempt to maximize the potential benefit and minimize the morbidity. Tumor thickness, presence or absence of ulceration, anatomical site of primary, and sex of the patient are all important criteria for estimating the risk of metastasis. The elderly and obese are more likely to suffer from long-term complications of lymphadenectomy, and therefore the risk and benefits must be meticulously evaluated before application of ELND in this patient population is undertaken.

Biopsy↗
PubMed1990

[Prevalence of risk factors for chronic diseases. A study in the general population of the metropolitan area, 1986-1987].

Risk factors for chronic diseases were studied in a random sample of 475 males and 728 females from the Metropolitan area of Santiago. A questionnaire was used to estimate the consumption of alcohol and tobacco and the level of physical activity. Weight and height were measured and socio-economic situation was classified according to Graffar. Prevalence rates for males and females were: hypertension 8.6 and 9.1%; obesity 13.2 and 22.7%; present sokers 50.7 and 43.4%; sedentarism 75.6 and 86.9%; alcohol consumption 56.2 and 19.8%. Thus, women show higher rates than males for hypertension, obesity and sedentarism. They smoked as much as males and consumed less alcohol. Among women a higher prevalence of obesity, alcohol consumption and sedentarism was observed in lower socio-economic classes. Among males, only sedentarism was more prevalent in lower socio-economic classes. The number of risk factors present was 1 in 28.6% of the population; 2 in 40.1%; 3 in 22.1%; 4 in 3.7% and 5 in 0.1%. Absence of risk factors was observed in only 5.4% of the population. The present data may help to design preventive strategies for diseases related to these risk factors.

Adolescent↗
PubMed1985

Phospholipase activities of the P388D1 macrophage-like cell line.

The murine macrophage (M phi) cell line, P388D1, was employed as a source of M phi phospholipases in order to characterize the enzymatic properties and subcellular localization of these enzymes because of their importance for prostaglandin biosynthesis. Phospholipase activity was assessed with dipalmitoylphosphatidylcholine (DPPC) as substrate. Phospholipases were characterized with respect to divalent cation dependence, pH optima, and localization in subcellular compartments using linear sucrose gradients. By these criteria a number of different phospholipases were identified. Most importantly, a single Ca2+-dependent activity with a pH optimum of 8.8 was identified in membrane-rich fractions (plasma membrane, mitochondria, and endoplasmic reticulum) and could be clearly separated from the remaining activities, which are Ca2+ independent and exhibit pH optima of 7.5, 5.1, and 4.2. The phospholipases with acidic pH optima may be associated with subcellular components containing lysosomal enzymes and both phospholipase A1 and phospholipase A2 activities are observed. In contrast, the phospholipase activity with a pH optimum of 7.5 sediments with the cytosolic proteins and is inhibited by 5 mM Ca2+. No significant phospholipase C activity was detected in assays performed with or without added Ca2+ at pH's 4.2, 5.1, 7.5, or 8.8 using DPPC as substrate. However, the P388D1 cells do contain a lysophospholipase that is at least 20 times more active than the phospholipase A activities identified. Its presence must be taken into account in evaluating the positional specificities and properties of the macrophage phospholipases.

Animals↗
PubMedDate not supplied

Surgical management of stage I and II melanoma patients: approach to the regional lymph node basin.

The role for elective lymph node dissection in the management of clinically localized (Stage I and II) melanoma patients represents a long-standing controversy. Contemporary randomized elective lymph node dissection trials have been completed with recently presented results demonstrating some survival benefit for surgical therapy of micrometastases in specific subsets of patients. Lymphatic mapping and sentinel node biopsy offers a rational alternative to elective lymph node dissection for all high risk Stage I and II melanoma patients. Recent advances in lymphatic mapping techniques have resulted in improved identification of the sentinel node. Combined with advances in histologic evaluations of lymph nodes, accurate and minimally invasive mechanisms for assessing lymph node status are now available. This latter goal is critical in light of recently published data demonstrating improved survival with the use of high dose interferon alpha administered in the adjuvant setting for patients with nodal metastases.

Biopsy↗
PubMedDate not supplied

Presentation, treatment, and outcome of local recurrence afterskin-sparing mastectomy and immediate breast reconstruction.

BACKGROUND: The local recurrence (LR) rate with skin-sparing mastectomy (SSM) and immediate breast reconstruction (IBR) has been reported as comparable to the LR rate after conventional mastectomy. However, limited data are available on the prognostic significance and management of LR following SSM. METHODS: A prospective database maintained at the University of Texas M. D. Anderson Cancer Center identified 437 SSMs performed for 372 invasive T1/T2 breast cancers between 1986 and 1993. RESULTS: Twenty-three LRs were identified, with a LR rate of 6.2% (23/372). Twenty-two of these (96%) presented as palpable skin-flap masses. The median time to recurrence was 25 months (range, 3 to 98 months). Fourteen patients were treated with a combination of surgery and systemic therapy. Resection of the reconstructed breast was performed in only three patients. Complete local control of the recurrent disease was achieved in 17 patients (74%). Nine patients (39%) developed distant metastatic disease. At a median follow-up of 26 months, 14 of 23 patients (61%) are alive without evidence of disease, and 7 (30%) have died from breast cancer. CONCLUSIONS: Because LR rate with SSM is low and likelihood of local control and survival is high, SSM and IBR is an acceptable treatment option for early stage breast cancer.

Adult↗
PubMedDate not supplied

Local rotational flaps for breast conservation therapy as an alternative to mastectomy.

BACKGROUND: An anticipated poor cosmetic result has traditionally been deemed a relative contraindication for breast conservation therapy (BCT). We sought to determine whether a local rotational flap could achieve satisfactory cosmesis in patients who were anticipated to have a poor cosmetic result following standard segmental mastectomy but who nevertheless desired BCT. METHODS: Within the past 3 years, nine patients were treated with BCT using local rotational flap techniques. Their records were reviewed for patient characteristics, pre- and postoperative treatment, disease-free status, and patient satisfaction with cosmesis. RESULTS: The cosmetic outcome following a segmental mastectomy was anticipated to be unacceptable due to the following features: a large previous biopsy cavity with unknown or positive margins (three patients); initial large primary tumors with unknown extent of residual disease following induction chemotherapy (five patients); and pre-existing poor cosmesis (one patient). One patient had refused modified radical mastectomy and had satellitosis from inadequately treated primary tumor (excisional biopsy with positive margins and no further therapy). The median initial tumor size was 2.7 cm (range, 1.5 cm to 5.0 cm). Final resection margins were negative in all patients. Postoperative radiotherapy was given in seven patients; one patient did not receive radiotherapy because of a pre-lupus condition and one did not require radiotherapy because her pathologic diagnosis was Paget's disease without an invasive component. Cosmesis was judged to be good to excellent by eight of nine patients. The patient who refused mastectomy was dissatisfied with cosmesis because of mild asymmetry. With a median follow-up of 24 months, only one patient has developed a local recurrence. CONCLUSION: Local rotational flaps composed of adjacent breast tissue are an acceptable method of achieving satisfactory cosmesis in selected patients who desire BCT.

Adult↗
PubMedDate not supplied

Lymphoscintigraphy as a predictor of lymphatic drainage from cutaneous melanoma.

BACKGROUND: If cutaneous lymphoscintigraphy (CL) is accurate in predicting the draining lymph node basins at risk from primary axial melanomas, then regional metastases should only occur in those lymph node basins identified by CL. METHODS: This study is a retrospective review of patients undergoing CL for primary axial melanomas from June 1, 1985, until June 31, 1992. Data retrieved included age, gender, number of basins identified, location of basins identified, management of basins, recurrence in lymphatics, development of distant disease, and long-term follow-up. RESULTS: A total of 181 patients underwent elective LND, and 48 patients (27%) had melanoma in the nodes within the dissected basin. Of these 181 patients, seven developed nodal metastases as their site of first recurrence. All seven recurrences were seen at sites dissected or at sites indicated by CL, which the primary surgeon elected not to treat initially. Of the 116 patients observed, 16 (14%) developed lymph node metastases as their first site of recurrence. Fifteen of these 16 patients had their site of lymph node metastases predicted by CL. In this study, CL predicted 98.6% of all lymph node metastases. CONCLUSIONS: The high overall reliability of CL as demonstrated by long-term follow-up indicates that the information obtained by CL can be reliably used to guide intervention. Initial evaluation of patients with high-risk cutaneous melanomas at sites with ambiguous lymphatic drainage must include CL in order to determine the draining lymph node basins and to plan therapy.

Adolescent↗
PubMedDate not supplied

Feasibility of breast conservation therapy in metachronous or synchronous bilateral breast cancer.

BACKGROUND: The optimal management of contralateral breast cancer (CC) in patients previously treated with breast-conserving therapy (BCT) is unclear, as is whether these patients continue to choose BCT as the preferred treatment of their second breast cancer. METHODS: Of 1328 patients treated with BCT at The University of Texas M. D. Anderson Cancer Center between 1958 and 1994, 63 developed a contralateral breast cancer. We reviewed the charts of these patients retrospectively, and standard demographic and treatment variables were evaluated. Survival was analyzed by the Kaplan-Meier method and subgroups by chi2 analysis. RESULTS: Twenty-nine percent of the patients had a family history of breast cancer. First breast cancers were detected by patient or physician in 67% of cases and by mammogram in 17% of cases, compared to 59% and 36%, respectively, of CC (P = .04). Median time to development of CC was 61 months. Sixty percent of the initial tumors were AJCC stage 0 or I with a median size of 2 cm, whereas 74% of the CC were stage 0 or I (P = .02), with a median size of 1.5 cm. Eighty-seven percent of patients chose BCT for treatment of CC. There were few treatment-related complications. Recurrence rates were not significantly different from those of patients undergoing BCT for the initial cancer (P = .47), and 5- and 10-year actuarial survival rates after the first cancer were 93% and 76%, respectively. Median follow-up was 134 and 56 months from the time of diagnosis of the initial cancer and CC, respectively. CONCLUSIONS: Because contralateral breast cancer often is detected at an early stage, there are few treatment-related complications, and the risk of recurrence is no different from that for the initial cancer, BCT is an acceptable and desirable option for appropriately selected patients with metachronous or synchronous bilateral breast cancers.

Adult↗
PubMedDate not supplied

Local recurrence and survival among black women with early-stage breast cancer treated with breast-conservation therapy or mastectomy.

BACKGROUND: Black women with breast cancer have significantly worse survival rates and receive diagnoses at relatively younger ages, compared with white patients with breast cancer, in the United States. Young age at diagnosis has been associated with increased risk for local recurrence (LR) after breast-conservation therapy (BCT). The goal of this study was to evaluate the impact of age and BCT on LR and survival rates among black patients with breast cancer. METHODS: The records for 363 black women treated for breast cancer (excluding stage IV disease) at a comprehensive cancer center were reviewed. RESULTS: Fifty-eight percent of patients (n = 211) had tumors < or = 5 cm in diameter. Forty-two of these patients (19.9%) received BCT; the LR rate for this group was 9.8%. A total of 168 patients (79.6%) underwent mastectomy; the LR rate for this group was 8.9%. Data on the primary operation were unavailable for one patient. Five-year disease-free survival rates were similar for patients treated with BCT and those treated with mastectomy (88% and 73%, respectively). LR was associated with significant decreases in 5-year overall survival rates for both the BCT group (67% vs. 95%, P < .01) and the mastectomy group (43% vs. 76%, P < .01). LR and 5-year disease-specific survival rates were similar for patients <50 years of age and patients > or = 50 years of age, regardless of treatment. CONCLUSIONS: LR and survival rates are not compromised by the use of BCT among black American patients. LR is associated with an increased risk of breast cancer death, regardless of treatment type. Younger age at diagnosis was not associated with an increased rate of LR after BCT in this series.

Adolescent↗
PubMedDate not supplied

Recent advances in melanoma staging and therapy.

BACKGROUND: Recent advances in the staging and treatment of melanoma were reviewed. METHODS: A literature-based review was performed. RESULTS: The current American Joint Committee on Cancer (AJCC) Staging system for melanoma has several drawbacks. Proposed changes in the staging system to take into account simplified tumor thickness categories, tumor ulceration, and the number (rather than size) of nodal metastases will allow stage groups with more uniform prognosis. The widespread application of sentinel lymph node biopsy for nodal staging allows accurate nodal staging with minimal morbidity. Reverse transcriptase-polymerase chain reaction (RT-PCR) is a very sensitive molecular staging test that may prove useful for identifying early metastatic disease. There is finally an effective adjuvant therapy for melanoma--interferon alfa-2b. Other adjuvant therapies, including melanoma vaccines, may provide effective and less toxic alternatives. New immunotherapy and gene therapy strategies are under investigation. CONCLUSIONS: Ongoing and future adjuvant therapy trials will benefit from improved melanoma staging by accrual of homogeneous groups of patients. New approaches for adjuvant therapy await completion of clinical trials. Innovative new therapies offer hope for patients with advanced disease.

Biopsy↗
PubMedDate not supplied

Feasibility of immediate breast reconstruction for locally advanced breast cancer.

BACKGROUND: Immediate breast reconstruction (IBR) has been considered contraindicated for patients with locally advanced breast cancer (LABC). Our goal was to determine whether IBR resulted in delayed postoperative chemotherapy, increased postoperative complications, or increased risk of recurrent disease. METHODS: A prospective database of 540 modified radical mastectomies performed with IBR between 1990 and 1993 identified 50 patients with LABC. Postoperative management and outcome were compared to that of 72 patients undergoing modified radical mastectomy without IBR treated on a standardized LABC protocol using preoperative chemotherapy, postoperative chemotherapy, and radiotherapy during the same time period. RESULTS: Results were evaluated by chi2 analysis. The median ages for the patients with IBR versus those not undergoing IBR were 44 and 46 years, respectively. The stage distribution for the IBR patients versus patients not undergoing IBR was as follows: IIB, 46% versus 17%; IIIA, 44% versus 39%; and IIIB, 10% versus 44%. The types of IBR were transverse rectus abdominis myocutaneous (TRAM) flap (68%), latissimus dorsi flap (2%), and implants (30%). Chemotherapy was given to all IBR patients: 24% preoperatively and 96% postoperatively. Radiotherapy was used in 40%. Four postoperative complications (8%) necessitated prolongation of hospitalization, including two patients requiring surgical debridement for partial flap loss; there were no complete flap losses. The incidences of major and minor wound complications in the group not undergoing IBR were 7% and 4%, respectively. Of the 15 patients receiving implant reconstruction, 7 (47%) required subsequent implant removal because of contractures or infections. The median interval between surgery and postoperative chemotherapy was 35 days for the IBR patients and 21 days for the patients not undergoing IBR. This difference was marginally significant (P =.05). With a median follow-up of 58.4 months, no significant differences in local or distant relapse rates were detected. CONCLUSIONS: IBR can be performed with low morbidity in patients with LABC. Use of autogenous tissue is preferable because of poor results with implants. IBR is associated with somewhat longer intervals to resumption of postoperative chemotherapy, but this does not appear to be clinically significant-the local and distant relapse rates are similar for LABC patients undergoing modified radical mastectomy with or without IBR.

Adult↗
PubMedDate not supplied

Immunological properties of melanoma tumor-infiltrating lymphocytes before and after IL-2-based biotherapies.

Immunological properties of melanoma TILs before and/or after IL-2-based biotherapies were investigated. TILs harvested before therapies, including those for adoptive transfer, proliferated well in culture with IL-2 and displayed cytotoxicity relatively restricted to autologous tumor cells. In contrast, TILs during or at the end of IL-2 based therapies did not proliferate in culture with IL-2. TILs from tumors even harvested 45 days after the end of IL-2 therapy modestly proliferated in culture with IL-2 and showed MHC-nonrestricted cytotoxicity. The number of live tumor cells that were yielded from melanomas during or at the end of IL-2-based therapies significantly decreased in all nine patients with metastatic melanomas, regardless of their clinical responses (2 PR, 2 MR, 2 SD, and 3 PD). Collectively, these results suggest that current IL-2-based therapies resulted in both transient nonresponsiveness of TILs to IL-2 and transient decrease in the number of live tumour cells in most melanoma patients.

Cell Count↗
PubMedDate not supplied

Selective lymphadenectomy: emerging role for lymphatic mapping and sentinel node biopsy in the management of early stage melanoma.

The percentage of melanoma patients diagnosed at an early stage is increasing. Many of these patients, particularly those with primary tumors thicker than 1.5 mm, harbor occult metastases in regional nodes and are eligible for regional lymphadenectomy as part of their primary management. Until the results of recently completed prospective randomized trials are available the role for elective lymphadenectomy in terms of survival benefit remains a controversial issue. A new technique, intraoperative lymphatic mapping and sentinel node biopsy, has emerged as a simple way to determine whether or not metastatic disease is present. An intradermal injection of a vital blue dye at the site of the primary tumor allows identification of a "sentinel" node in the regional basin. A study of 237 patients was recently reported by Morton et al. (Arch Surg 127:392-399, 1992; Surg Oncol Clin North Am 1:247-259, 1992) demonstrating that the sentinel node can be readily identified > 80% of the time and that histologic examination of the node results in at least a 95% accuracy rate in staging the nodal basin for metastases. Our present series substantiates the results of the original study. An international multicenter trial has been proposed to further confirm the accuracy and universal feasibility of this technique. Acceptance of this technique will lead to a selective approach to regional lymphadenectomy, as only patients with proven micrometastases will undergo lymph node dissections. This approach should satisfy both the advocates and the opponents of elective regional lymphadenectomy.

Biopsy↗
PubMedDate not supplied

Pathologic tumor response in the breast following neoadjuvant chemotherapy predicts axillary lymph node status.

PURPOSE: Neoadjuvant chemotherapy is becoming the standard of care for locally advanced breast cancer. This study was performed to determine whether pathologic primary tumor response to neoadjuvant chemotherapy might predict axillary lymph node status and so be used to identify patients in whom surgery could be effectively limited to biopsy of the previous primary tumor site without axillary dissection. PATIENTS AND METHODS: Between 1992 and 1996, 170 consecutive patients with locally advanced breast cancer were treated in a prospective trial with four preoperative cycles of 5-fluorouracil, doxorubicin, and cyclophosphamide. Disease was staged before initiation of preoperative chemotherapy and before surgery. Segmental resection with axillary lymph node dissection or modified radical mastectomy was performed first, followed by postoperative chemotherapy and radiation therapy of the breast (or chest wall) and regional lymphatics. Patient and tumor characteristics associated with complete versus incomplete pathologic primary tumor response to neoadjuvant chemotherapy and correlation between primary breast tumor pathologic response and axillary lymph node status found at surgery were analyzed. RESULTS: Of 156 evaluable patients, 30 patients (19%) had primary breast tumors that were completely eliminated after induction chemotherapy based on histologic assessment. Nineteen of those 30 patients (63%) had negative axillary lymph nodes at dissection, compared with 13 patients (33%) of the 40 who had a near-complete pathologic primary tumor response (< or = 1 cm3 remaining) and only 15 patients (17%) of the 86 who had > 1 cm3 tumor remaining in the pathology specimen of the breast primary. Of the 22 patients with a complete pathologic response in the breast and a clinically negative axilla after induction chemotherapy, axillary dissection revealed positive lymph nodes in four. These four patients had only one or two positive lymph nodes. DISCUSSION: Because initial clinical regression of primary tumor with neoadjuvant chemotherapy is considered an excellent prognostic indicator and because patients with locally advanced breast cancer routinely receive local and regional radiation treatment followed by additional chemotherapy, the role of breast and axillary surgery has been questioned. In this study, a complete pathologic response of the primary tumor to induction chemotherapy is highly predictive of negative axillary lymph node status. Therefore, axillary lymph node dissection may be omitted in certain subsets of patients who have a biopsy-proven complete pathologic response in the primary tumor and a clinical negative axillary examination. Further prospective, randomized investigation is needed to confirm this finding.

Adult↗