Activation in lectin-free interleukin 2 (IL-2) containing supernatants of peripheral blood mononuclear leukocytes (PBL) from cancer patients or normal individuals resulted in expression of cytotoxicity toward 20 of 21 natural killer (NK)-resistant fresh solid tumor cells tested. Fresh solid tumor cells were resistant to NK-mediated lysis in 10 autologous patients' PBL-tumor interactions, and from 17 normal individuals tested against 13 allogeneic fresh tumors. Culture of PBL in IL-2 for 2-3 d was required for the lymphokine activated killers (LAK) to be expressed, and lytic activity toward a variety of NK-resistant fresh and cultured tumor targets developed in parallel. Autologous IL-2 was functional in LAK activation, as well as interferon-depleted IL-2 preparations. Irradiation of responder PBL before culture in IL-2 prevented LAK development. Precursors of LAK were present in PBL depleted of adherent cells and in NK-void thoracic duct lymphocytes, suggesting that the precursor is neither a monocyte nor an NK cell. LAK effectors expressed the serologically defined T cell markers of OKT.3, Leu-1, and 4F2, but did not express the monocyte/NK marker OKM-1. Lysis of autologous fresh solid tumors by LAK from cancer patients' PBL was demonstrated in 85% of the patient-fresh tumor combinations. Our data present evidence that the LAK system is a phenomenon distinct from either NK or CTL systems that probably accounts for a large number of reported nonclassical cytotoxicities. The biological role of LAK cells is not yet known, although it is suggested that these cells may be functional in immune surveillance against human solid tumors.

https://rupress.org/jem/article-pdf/155/6/1823/1092516/1823.pdf

Lymphokine-activated killer cell phenomenon. Lysis of natural killer-resistant fresh solid tumor cells by interleukin 2-activated autologous human peripheral blood lymphocytes.

Histopathology is insufficient to predict disease progression and clinical outcome in lung adenocarcinoma. Here we show that gene-expression profiles based on microarray analysis can be used to predict patient survival in early-stage lung adenocarcinomas. Genes most related to survival were identified with univariate Cox analysis. Using either two equivalent but independent training and testing sets, or 'leave-one-out' cross-validation analysis with all tumors, a risk index based on the top 50 genes identified low-risk and high-risk stage I lung adenocarcinomas, which differed significantly with respect to survival. This risk index was then validated using an independent sample of lung adenocarcinomas that predicted high- and low-risk groups. This index included genes not previously associated with survival. The identification of a set of genes that predict survival in early-stage lung adenocarcinoma allows delineation of a high-risk group that may benefit from adjuvant therapy.

Gene-expression profiles predict survival of patients with lung adenocarcinoma

BACKGROUND
A frequent complication of anticancer treatment, oral and gastrointestinal (GI) mucositis, threatens the effectiveness of therapy because it leads to dose reductions, increases healthcare costs, and impairs patients' quality of life. The Multinational Association of Supportive Care in Cancer and the International Society for Oral Oncology assembled an international multidisciplinary panel of experts to create clinical practice guidelines for the prevention, evaluation, and treatment of mucositis.

METHODS
The panelists examined medical literature published from January 1966 through May 2002, presented their findings at two separate conferences, and then created a writing committee that produced two articles: the current study and another that codifies the clinical implications of the panel's findings in practice guidelines.

RESULTS
New evidence supports the view that oral mucositis is a complex process involving all the tissues and cellular elements of the mucosa. Other findings suggest that some aspects of mucositis risk may be determined genetically. GI proapoptotic and antiapoptotic gene levels change along the GI tract, perhaps explaining differences in the frequency with which mucositis occurs at different sites. Studies of mucositis incidence in clinical trials by quality and using meta-analysis techniques produced estimates of incidence that are presented herein for what to our knowledge may be a broader range of cancers than ever presented before.

CONCLUSIONS
Understanding the pathobiology of mucositis, its incidence, and scoring are essential for progress in research and care directed at this common side-effect of anticancer therapies. Cancer 2004;100(9 Suppl):1995–2025. © 2004 American Cancer Society.

https://acsjournals.onlinelibrary.wiley.com/doi/pdf/10.1002/cncr.20162

Perspectives on cancer therapy-induced mucosal injury: pathogenesis, measurement, epidemiology, and consequences for patients

Small Cell Lung Cancer

Lung cancer stands as the most important malignant neoplasm in the United States because of its high prevalence, increasing incidence, high rate of mortality, and great potential for prevention through the control of cigarette smoking. The World Health Organization (WHO) classification of lung cancer identifies four major types: squamous cell carcinoma, adenocarcinoma, large cell carcinoma, and small cell carcinoma. These tumors are commonly divided into two groups based on differences in their biology and treatment: small cell (SCLC) and non-small cell carcinomas (NSCLC). This review analyzes NSCLC with a strong emphasis on the practical aspects of treatment. We give recommendations about smoking cessation and early diagnosis through screening of high-risk individuals. We review contemporary diagnostic and staging techniques in the context of the new international TNM system of staging. Subsequent discussions of treatment are based on this new staging system. We stress the pivotal role of surgery for the management of local disease, and in addition present the potential contributions of newer radiation therapy techniques. We examine chemotherapy in detail, including a review of the comparative activity of the available cytotoxic agents against NSCLC, the relative contribution of combination chemotherapy, and the role of surgical adjuvant treatment with either chemotherapy or immunotherapy. We advise that patients with NSCLC be treated under the aegis of modern clinical trials of new therapy whenever possible. When this is not possible, we recommend an individualized approach based on such factors as the patient's age, general state of health, cardiopulmonary status, psychosocial status, and personal system of values.

Non-small cell lung cancer

The authors present prognostic information on recurrence and survival for resected Stage I lung cancer patients with squamous cell carcinoma, adenocarcinoma or large cell carcinoma. The data derive from 392 carefully staged patients and include results from the history and physical examination, preoperative laboratory tests, nature of the surgery, complications, initial pathologic findings following surgical resection, and final pathologic review. A simple multivariate model of recurrence, which is used to classify patients into low, intermediate, and high-risk groups, is based on tumor size and location (T1, T2), histologic type (squamous, nonsquamous/mixed) and nodal status (N0, N1). To model survival, the performance status and the presence of empyema, pneumonia, or wound infection were added to the previous factors. Not all factors associated with increased mortality are associated with increased risk of recurrence, and, in particular, postoperative empyema, pneumonia or wound infections carry an increased risk of death only. Serial measurements of performance status and leukocyte count have the potential for monitoring for increased risk of recurrence and death.

Prognostic factors in patients with resected stage I non-small cell lung cancer. A report from the Lung Cancer Study Group.

Small cell lung cancer: progress and perspectives.

Endodermal sinus tumor (EST) of the mediastinum is a rare germ-cell neoplasm affecting mainly young adult males. Ten patients with EST were treated with a multimodality approach that included surgery, chemotherapy, and radiotherapy. All patients had relapses after achieving a transient response except one who is still in complete remission more than five years following the diagnosis of the disease. Optimal therapy for this neoplasm has yet to be discovered. The disease is a subset of extragonadal germ cell tumors which appears to be lethal in most cases, particularly when the primary tumor is unresectable. The first case of five-year disease-free survival is described.

Endodermal sinus tumor of the mediastinum

Cancer and the kidney: Renal complications of neoplasms

Cushing's syndrome with small cell carcinoma of the uterine cervix

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