Open-label phase II study of the efficacy of nivolumab for cancer of unknown primary.

BACKGROUND: Cancer of unknown primary (CUP) has a poor prognosis. Given the recent approval of immune checkpoint inhibitors for several cancer types, we carried out a multicenter phase II study to assess the efficacy of nivolumab for patients with CUP. PATIENTS AND METHODS: Patients with CUP who were previously treated with at least one line of systemic chemotherapy constituted the principal study population. Previously untreated patients with CUP were also enrolled for exploratory analysis. Nivolumab (240 mg/body) was administered every 2 weeks for up to 52 cycles. The primary endpoint was objective response rate in previously treated patients as determined by blinded independent central review according to RECIST version 1.1. RESULTS: Fifty-six patients with CUP were enrolled in the trial. For the 45 previously treated patients, objective response rate was 22.2% [95% confidence interval (CI), 11.2% to 37.1%], with a median progression-free survival and overall survival of 4.0 months (95% CI, 1.9-5.8 months) and 15.9 months (95% CI, 8.4-21.5 months), respectively. Similar clinical benefits were also observed in the 11 previously untreated patients. Better clinical efficacy of nivolumab was apparent for tumors with a higher programmed death-ligand 1 expression level, for those with a higher tumor mutation burden, and for microsatellite instability-high tumors. In contrast, no differences in efficacy were apparent between tumor subgroups based on estimated tissue of origin. Adverse events were consistent with the known safety profile of nivolumab. No treatment-related death was observed. CONCLUSIONS: Our results demonstrate a clinical benefit of nivolumab for patients with CUP, suggesting that nivolumab is a potential additional therapeutic option for CUP.

Internal Delensing of Cosmic Microwave Background Polarization B-Modes with the POLARBEAR Experiment.

Using only cosmic microwave background polarization data from the polarbear experiment, we measure B-mode polarization delensing on subdegree scales at more than 5σ significance. We achieve a 14% B-mode power variance reduction, the highest to date for internal delensing, and improve this result to 22% by applying for the first time an iterative maximum a posteriori delensing method. Our analysis demonstrates the capability of internal delensing as a means of improving constraints on inflationary models, paving the way for the optimal analysis of next-generation primordial B-mode experiments.

A phase II dose-ranging study of palonosetron in Japanese patients receiving moderately emetogenic chemotherapy, including anthracycline and cyclophosphamide-based chemotherapy.

BACKGROUND: The 5-HT(3) receptor antagonists (RAs) help maintain the standard of care, in various combinations with other agents, for prevention of chemotherapy-induced nausea and vomiting (CINV). Palonosetron is a new generation 5-HT(3) RA with indication not only acute but also delayed nausea and vomiting induced by moderately emetogenic chemotherapy (MEC). This study was carried out to determine the optimal dosage of palonosetron in combination with dexamethasone in patients in Japan. PATIENTS AND METHODS: This study evaluated the efficacy and safety of palonosetron in patients receiving MEC combined with dexamethasone. Patients received single doses of 0.075, 0.25, or 0.75 mg of palonosetron before MEC. Dexamethasone was infused before palonosetron, at 20 mg for the patients receiving paclitaxel (Taxol) and 8 mg for the patients not receiving paclitaxel. The primary end point was complete response (CR: no emetic episodes and no rescue medication) in the acute phase (0-24 h). RESULTS: In total, 204 patients (88 men, 116 women; 96 with paclitaxel, 108 without paclitaxel) were assessable for efficacy. No dose-response relationship was observed regarding the CR rate in the acute phase. CR rates increased dose dependently for delayed (24-120 h) and overall (0-120 h) phases in patients receiving anthracyclines and cyclophosphamide combination (AC/EC, n = 80); however, the difference in CR rates among doses was not statistically significant. The most commonly reported adverse events related to palonosetron were constipation and headache, confirming the class safety profile. CONCLUSION: This study indicates a statistically nonsignificant trend for the dose-response relationship for antiemetic protection in the delayed and overall phases in AC/EC patients (the regimen currently considered to be more emetogenic than MEC).

A phase II study of palonosetron combined with dexamethasone to prevent nausea and vomiting induced by highly emetogenic chemotherapy.

BACKGROUND: This is a randomized, double-blind, dose-ranging study in patients receiving highly emetogenic chemotherapy (HEC) to evaluate the safety, efficacy, and pharmacokinetics of palonosetron, in combination with dexamethasone. MATERIALS AND METHODS: We randomized 233 patients to receive palonosetron as a single i.v. bolus dose of 0.075, 0.25, or 0.75 mg before administration of HEC. Dexamethasone (12-16 mg i.v. on day 1, 8 mg i.v. on day 2, and 4-8 mg i.v. on day 3) was administered for prophylactic antiemesis. Pharmacokinetics of palonosetron was analyzed in 24 patients. RESULTS: In this study, all patients were given > or =50 mg/m(2) cisplatin, which was considered to be HEC. No significant differences in complete response (CR: no emesis and no rescue medication) rates were found in the first 24 h between the 0.075-, 0.25-, and 0.75-mg groups (77.6%, 81.8%, and 79.5%, respectively). In the 120-h period of overall observation, CR rates increased in a dose-dependent manner. In the 0.75-mg group, we observed a significantly longer time to treatment failure than in the 0.075-mg group (median time >120 versus 82.0 h, P = 0.038). Palonosetron was tolerated well and did not show any dose-related increase in adverse effects. CONCLUSIONS: Palonosetron at doses of 0.25 and 0.75 mg was shown to be effective in preventing chemotherapy-induced nausea and vomiting with high CR rates of patients treated with HEC in Japan. All tested doses of palonosetron were tolerated well.

Impact of double-balloon endoscopy on the diagnosis of jejunoileal involvement in primary intestinal follicular lymphomas: a case series.

In recent years, primary gastrointestinal follicular lymphoma has been increasingly detected in the duodenum on esophagogastroduodenoscopy (EGD). Primary gastrointestinal follicular lymphomas are frequently distributed to multiple sites in the gastrointestinal tract. Therefore, investigation into the spread of follicular lymphomas in the small bowel is important in order to determine the most appropriate treatment strategy. The performance of double-balloon endoscopy (DBE) in the diagnosis of jejunoileal follicular lymphoma lesions has not been fully evaluated. We aimed to investigate the value of DBE in addition to computed tomography (CT) and (18)F-fluorodeoxyglucose positron emission tomography ((18)F-FDG-PET) in the diagnosis of jejunoileal follicular lymphoma. DBE with biopsy was performed in seven patients with primary duodenal follicular lymphoma diagnosed by EGD, in order to investigate jejunoileal involvement. Jejunoileal follicular lymphoma lesions were detected by DBE in six out of the seven patients (three in the jejunum and three in the jejunum and ileum), whereas CT and (18)F-FDG-PET failed to detect the existence of these lesions. Endoscopic findings of the jejunoileal lesions revealed multiple white nodules and white villi, which were similar to those of duodenal lesions. DBE was more useful for the diagnosis of jejunoileal involvement in primary intestinal follicular lymphoma than CT and (18)F-FDG-PET. The use of DBE will become important for determining the most appropriate treatment for gastrointestinal follicular lymphoma.

Overexpression of inducible nitric oxide synthase and accumulation of 8-OHdG in nasopharyngeal carcinoma.

AIMS: Nitric oxide (NO), produced by inducible NO synthase (iNOS), has been suggested to cause oxidative stress, leading to 8-hydroxydeoxyguanosine (8-OHdG) accumulation and subsequent transversion mutation of DNA. The aim was to evaluate iNOS expression and the status of oxidative stress in nasopharyngeal carcinoma (NPC). METHODS AND RESULTS: Seventy-three cases of NPC were investigated to examine the immunohistochemical expression of iNOS, 8-OHdG and latent membrane protein-1 (LMP-1) and Epstein-Barr virus-encoded small RNA (EBER) expression using in situ hybridization. iNOS mRNA expression and p53 gene mutations were also assessed. Overexpression of iNOS, LMP-1 and EBER was observed in 62 (84.9%), 28 (38.4%) and 53 (72.6%) cases respectively. p53 gene mutation was found in 10 of 73 (13.7%) cases. Immunohistochemical iNOS expression was associated with the 8-OHdG labelling index, iNOS mRNA expression and p53 gene alteration (P < 0.0001, P = 0.016 and 0.0082 respectively). CONCLUSIONS: Our present findings suggest that the expression of iNOS induces oxidative stress in NPC. Although the presence of p53 mutation was associated with iNOS overexpression, the type of acid-base change of p53 was transition, but not transversion, which suggests that the p53 gene is not the direct target of DNA damage by 8-OHdG accumulation.

Comparison in prognosis after VATS lobectomy and open lobectomy for stage I lung cancer: retrospective analysis focused on a histological subgroup.

BACKGROUND: Video-assisted thoracoscopic surgery (VATS) has become an attractive surgical procedure, but several issues remain to be resolved. Prognosis after VATS lobectomy is important to evaluate the adequacy of VATS lobectomy as a cancer operation. Interestingly, several investigators, including us, have reported that prognosis after VATS lobectomy was superior to that after open lobectomy in early non-small-cell lung cancer (NSCLC). One of the possible reasons is the low invasiveness of VATS lobectomy. But we considered that patient bias might have some influence favoring VATS lobectomy. To evaluate our hypothesis, we reviewed medical records of stage I NSCLC patients undergoing operation between 1993 and 2002. We compared and evaluated the relationship between patient characteristics and prognosis after VATS and open lobectomy. We focused particularly on histological type, classifying it into four subgroups; (1) bronchioloalveolar carcinoma (BAC), (2) mixed BAC + papillary adenocarcinoma (BAC + Pap), (3) other adenocarcinoma (Other adeno), (4) squamous cell carcinoma + others (Sq + others). RESULTS: A total of 165 patients underwent VATS lobectomy, and 123 patients underwent open lobectomy. The 5-year survival rate of the VATS lobectomy group was 94.5% and that of the open lobectomy group was 81.5%. Univariate Cox regression of survival revealed that male, CEA > 5, Other adeno, Sq + others, open lobectomy, and tumor size > 3 cm were significant negative prognostic variables. Multivariate Cox regression of survival revealed that histological subtype and tumor size were independent prognostic factors, but surgical procedure was not an independent prognostic factor. COMMENTS: Prognosis after VATS lobectomy was superior to that after open lobectomy, but patient bias influenced the prognosis in favor of VATS lobectomy, and the surgical procedure itself was not a prognostic factor.

Real-time PCR method for quantification of Staphylococcus aureus in milk.

A reproducible real-time PCR method that targets the putative transcriptional regulator gene of Staphylococcus aureus was developed to quantify this microorganism in milk samples. On the basis of partial sequences of this gene determined from S. aureus strains, we designed the specific primers and probe for use in a quantitative PCR assay. These specificities were confirmed with 25 strains of S. aureus and 35 strains of other bacteria. A real-time PCR assay with serial 10-fold dilutions of purified DNA and pure culture was conducted. It was possible to construct standard curves with a high correlation coefficient (r2 = 0.99) in the range of 50 ng to 50 fg for purified DNA and 10(7) to 10(1) CFU/ml for a pure culture. The constructed standard curve for milk samples was similar to that for the pure culture, and the quantification of S. aureus in the range of 10(7) to 10(1) CFU/ml was possible. Moreover, to determine how our real-time PCR method would perform under actual analytical conditions, we quantified the DNA from S. aureus after two types of heat treatments were used for the pasteurization of milk. The amount of DNA found was affected after heat treatment at 63 degrees C for 30 min (low-temperature long-time method) but not at 72 degrees C for 15 s (high-temperature short-time method). The results indicate that the real-time PCR method developed in this study is effective for monitoring S. aureus contamination in milk because of its high specificity and sensitivity.

Exotic radiation from a photonic crystal excited by an ultrarelativistic electron beam.

We report the observation of an exotic radiation (unconventional Smith-Purcell radiation) from a one-dimensional photonic crystal. The physical origin of the exotic radiation is direct excitation of the photonic bands by an ultrarelativistic electron beam. The spectrum of the exotic radiation follows photonic bands of a certain parity, in striking contrast to the conventional Smith-Purcell radiation, which shows solely a linear dispersion. Key ingredients for the observation are the facts that the electron beam is in an ultrarelativistic region and that the photonic crystal is finite. The origin of the radiation was identified by comparison of experimental and theoretical results.

Salmonella prevalence and total microbial and spore populations in spices imported to Japan.

A total of 259 samples of 40 types of spices were tested for Salmonella prevalence and total microbial and spore populations. Salmonella enterica serotypes Weltevreden and Senftenberg were isolated from a black- and red-pepper sample, respectively. Because Salmonella was not detected by the most-probable-number method, it indicated that at least one cell of the microorganism was present in 25 g of sample. The mean aerobic bacterial count was greater than 5.39 log CFU/g in turmeric, garam masala, curry powder, and paprika. The mean bacterial spore counts were greater than 4.33 log CFU/g in turmeric and curry powder. The mean aerobic bacterial count in the two Salmonella-isolated samples was 6.93 log CFU/g. These results indicate that spices can be a source of contamination in the products where they are used as ingredients, and methods to reduce the microbial load in spices should be used.

Characterization of protein phosphorylation of the cytosol of AH-66 hepatoma ascites cells.

Endogenous phosphorylation reaction of the cytosol fraction of AH-66 hepatoma ascites cells in vitro was compared with that of normal rat liver. Cytosolic proteins with molecular weights of 125,000, 98,000, and 40,000 of AH-66 cells were heavily phosphorylated in a cyclic adenosine 3':5'-monophosphate-independent manner, but no counterpart was detected in normal liver cytosol. In order to examine whether these phosphoproteins were specifically present in AH-66 cytosol, cyclic adenosine 3':5'-monophosphate-independent protein kinases which phosphorylate these phosphoproteins were partially purified from AH-66 and liver cytosol by successive chromatography. Both kinase preparations were essentially free of endogenous protein substrates and catalyzed the phosphorylation of exogenous substrates, such as casein and phosvitin, but not histone and protamine. Both kinases markedly catalyzed the phosphorylation of the Mr 125,000, 98,000, and 40,000 proteins in AH-66 cytosol. The Mr 125,000, 98,000 and 40,000 proteins in liver cytosol were less intensely phosphorylated by the addition of the kinase from AH-66 cytosol. From these results, we conclude that these phosphoproteins are present in both AH-66 cytosol and liver cytosol but are highly concentrated in AH-66 cytosol.

Changes in urinary deoxypyridinoline level and vertebral bone mass in the development of adjuvant-induced arthritis in rats.

This study was designed to determine the effect of bone resorption on the development of generalized osteopenia in adjuvant-induced arthritic rats. Thirty of a total of sixty male SD rats, 6 weeks of age, were injected with killed mycobacterium butyricum suspended in mineral oil into the right hind paw and assigned to six groups of 5 animals each. The other thirty animals served as the age-matched noninjected controls. Animals were sacrificed at 4, 7, 10, 14, 21, and 28 days post-injection after measuring the bilateral hind-paw volumes. Twenty-four-hour urinary samples were obtained before sacrifice and the levels of deoxypyridinoline (D-Pyr) and creatinine (CR) were measured. Plasma intact osteocalcin levels were measured by a sandwich enzyme immunoassay at the start, 14 and 28 days after injection. Bone mineral measurement and histomorphometrical analyses were performed on specimens of the third lumbar vertebral body. On the seventh day after injection, arthritic rats showed significant decreases in the values of bone mineral content (BMC) and density (BMD) when compared to controls. Urinary D-Pyr/Cr ratios, however, did not increase on the seventh day, showing a significant increase on the tenth day after injection. The serum osteocalcin level was significantly reduced on the fourteenth day. The trabecular bone volume (BV/TV) in the arthritic rats showed a significant decrease from the seventh day. The trabecular thickness (Tb.Th) value significantly decreased on the seventh day after injection.(ABSTRACT TRUNCATED AT 250 WORDS)

Methotrexate maintains bone mass by preventing both a decrease in bone formation and an increase in bone resorption in adjuvant-induced arthritic rats.

We examined the effects of low doses methotrexate (MTX) and indomethacin (IND) on bone mass and turnover in normal male Sprague-Dawley rats and those with adjuvant-induced arthritis. Normal and the adjuvant (heat-killed mycobacterium)-injected rats, 6 weeks of age, were given MTX at daily doses of 0.05, 0.1, or 0.2 mg/kg body weight (BW) or IND at a daily dose of 1.0 mg/kg BW. Rats were killed at the start, or at 14 and 28 days. In normal rats, the administration of these agents did not change the lumbar and femoral BMD values, nor did the serum osteocalcin or urinary deoxypyridinoline (D-Pyr) levels. Lumbar trabecular osteoclast number (Oc.N/BS) and osteoclast surface (Oc.S/BS) were decreased in the rats given IND. In the arthritic rats, the administration of MTX did not prevent an early increase of paw edema in the adjuvant-injected limb, but late inflammatory edema was alleviated in the non-injected limb. However, MTX administration at a dose of 0.1-0.2 mg/kg BW maintained an age-dependent increase in the lumbar and femoral BMD values. While serum osteocalcin levels were decreased and urinary D-Pyr values were increased in the arthritic control rats, these bone markers remained at the levels of the normal rats. Decreases in mineral apposition rate (MAR) and bone formation rate (BFR/BS) and increases in the trabecular Oc.N/BS and Oc.S/BS values were prevented by MTX. While IND almost completely prevented inflammatory paw edema, it did not improve the parameters of bone formation. An increase in osteoclasts was prevented and the osteopenia in the lumbar and the femoral bone was only partially prevented by IND. These data suggest that MTX improves bone mass and turnover in the arthritic rat, in which several cytokines that affect bone cells are involved. An increase in bone resorption may be due to prostaglandins, but bone formation defect was suggested to be due to other cytokines such as IL-1, IL-6, and TNF-alpha in this model.

Risk factors for development of radiation pneumonitis following radiation therapy with or without chemotherapy for lung cancer.

PURPOSE: To determine the risk factors contributing to development of radiation pneumonitis (RP) in patients with lung cancer who undergo radiation therapy to the thorax. METHODS AND MATERIALS: Development and severity of RP were retrospectively analyzed for 89 patients with lung cancer who underwent radiation therapy with or without chemotherapy at the National Shikoku Cancer Center Hospital between 1991 and 1995. The severity of RP was determined using a modified grading scale based on that of the Radiation Therapy Oncology Group and the European Organization for the Research and Treatment of Cancer. RESULTS: Fifty-two (58%) patients developed RP: 34 patients with Grade 1, 5 with Grade 2, 8 with Grade 3, and 5 with Grade 5 RP. Severe RP tended to develop earlier than less severe RP, but not to a significant extent (p = 0.151). On logistic regression analysis including both patient condition and treatment factors, development of Grade 1 or more severe RP was most frequently observed for Stage I-II disease (p = 0.011). The use of chemotherapy, large daily radiation dose, and once-daily fractionation (vs. twice-daily fractionation) were possibly related to the development of RP (p = 0.057, p = 0.069, and p = 0.092, respectively). For the group of 48 patients who underwent chemoradiation therapy, the use of large daily radiation dose was a significant risk factor for RP (p = 0.014). In addition, the use of once-daily fractionation was a marginally significant risk factor (p = 0.052). Among chemotherapy drugs administered, cisplatin was a favorable factor (p = 0.011), while adriamycin was a risk factor (p = 0.061). CONCLUSIONS: In radiation therapy for lung cancer, administration of a large daily dose should be avoided in order to prevent RP, particularly when radiation therapy is combined with chemotherapy.

Bronchiolitis obliterans organizing pneumonia syndrome in breast-conserving therapy for early breast cancer: radiation-induced lung toxicity.

PURPOSE: Breast-conserving surgery and postoperative radiotherapy have played important roles in the treatment of early breast cancer. Bronchiolitis obliterans organizing pneumonia (BOOP) syndrome has recently been reported to be one of the complications of adjuvant radiotherapy. The purpose of this study was to determine the incidence of and risk factors for BOOP syndrome in breast cancer patients. METHODS AND MATERIALS: Between January 1996 and December 1998, 157 patients with breast cancer underwent radiotherapy after breast-conserving surgery. The criteria used for the diagnosis of BOOP syndrome were as follows: 1) radiation therapy to the breast within 12 months, 2) general and/or respiratory symptoms lasting for at least 2 weeks, 3) radiographic lung infiltrates outside the radiation port, and 4) no evidence of a specific cause. RESULTS: BOOP syndrome developed in 4 (2.5%) patients, who had fever and nonproductive cough, with patchy infiltrative shadows on chest roentgenograms which emerged between 5 and 6 months after radiotherapy. The symptoms and pulmonary infiltrates were rapidly improved by treatment with prednisone (40 mg/day), which was tapered over 2- to 5-month periods. However, BOOP syndrome relapsed in all cases during the tapering period or after withdrawal of prednisone. The eosinophil and neutrophil counts were increased and the ratios of CD4+ to CD8+ lymphocytes were elevated in bronchoalveolar lavage fluid in all four cases. There were no differences in proportions of patients by age, irradiated breast site, use of tamoxifen and/or chemotherapy, or radiation dose between those with and without BOOP syndrome. CONCLUSIONS: BOOP syndrome is considered an intractable form of lung toxicity after radiotherapy to the breast. An immunologic reaction mediated by eosinophils, neutrophils, and lymphocytes may be responsible for the development of this syndrome. Methods of prevention of BOOP syndrome should be established.

Two types of K+ currents modulated by arachidonic acid in bovine corneal epithelial cells.

PURPOSE: Fenamate sensitivity of the large-conductance K+ current in the corneal epithelium suggests that K+ transport could be modulated by arachidonic acid (AA) and/or its metabolites, which also regulate corneal epithelial migration. The main purpose of this study was to investigate AA-induced modulation of K+ currents expressed in the bovine corneal epithelium. METHODS: Freshly isolated bovine corneal epithelial cells were perfused with Ringer solution. Whole-cell currents were recorded by using either the conventional whole-cell-patch or the perforated-patch configuration. RESULTS: Two distinct types of K+ currents dominated the whole-cell current. The first was a voltage-gated K+ current that was inactivated completely by membrane depolarization. The inactivating voltage-gated K+ current was largest in presumptive basal cells. The second was a noisy, sustained K+ current that was never inactivated and seemed to be a counterpart of the large-conductance K+ current reported in the rabbit corneal epithelium. External application of AA (5-20 microm) inhibited the inactivating voltage-gated K+ current and augmented the noisy, sustained K+ current. Identical dual modulation was induced by other fatty acids (e.g., palmitoleic acid) that are not substrates for enzymes in the AA cascade. CONCLUSIONS: An inactivating voltage-gated K+ channel was identified for the first time in the corneal epithelium. AA and some fatty acids may directly activate the large-conductance K+ channel to augment its housekeeping functions in corneal epithelial cells.

Serum hepatocyte growth factor/scatter factor levels in small cell lung cancer patients.

Serum hepatocyte growth factor/scatter factor (HGF/SF) levels were measured in 25 patients with small cell lung cancer (SCLC), 16 patients with benign lung diseases and 15 healthy subjects with an enzyme-linked immunosorbent assay. The patients with SCLC did not have bacterial or interstitial pneumonia. Patients with benign lung diseases included eight with bacterial pneumonia, three with interstitial pneumonia, and five with benign lung tumor. Serum HGF/SF levels were significantly higher in patients with SCLC (mean +/- S.D.: 0.40 +/- 0.17 ng/ml) than in healthy subjects (0.26 +/- 0.093 ng/ml) (P = 0.0083). Patients with bacterial pneumonia had significantly higher serum HGF/SF (0.52 +/- 0.19 ng/ml) than did those with benign lung tumors (0.27 +/- 0.058 ng/ml) and healthy subjects (P = 0.013 and P = 0.0019, respectively). By clinical stage of SCLC, HGF/SF levels were 0.34 +/- 0.12 and 0.47 +/- 0.20 ng/ml in patients with limited disease and extensive disease, respectively; this difference was not significant (P = 0.080). Although serum HGF/SF levels were increased in patients with SCLC, this increase might not have been related to tumor burden.

Serum CD44 levels in patients with non-small cell lung cancer and their relationship with clinicopathological features.

Serum CD44 standard and CD44 variant 6 levels were measured in 45 non-small cell lung cancer (NSCLC) patients and 33 patients with benign lung disease by enzyme-linked immunosorbent assay (ELISA). Expression of CD44 variant 6 in trans-bronchial biopsy specimens from the NSCLC patients was studied by an immunoperoxidase method. CD44 standard and CD44 variant 6 levels in NSCLC patients were not significantly different from those in benign lung disease patients. However, serum CD44 variant 6 level in squamous cell carcinoma patients (226.8 +/- 152.7 ng/ml) was significantly higher than in patients with benign lung disease (154.8 +/- 46.4 ng/ml) (P = 0.011). Neither the serum level of CD44 standard nor that of CD44 variant 6 was correlated with disease Stage and metastasis. CD44 variant 6 expression was most frequently observed in squamous cell carcinoma (P = 0.00058); 15 (79%) of 19 squamous cell carcinoma cases were positive, as were five (22%) of 23 adenocarcinoma cases and two (67%) of three large cell carcinoma cases. Serum CD44 variant 6 levels were 217.1 +/- 143.1 and 156.1 +/- 48.8 ng/ml in patients with and without positive expression of CD44 variant 6, respectively (P = 0.020). Serum CD44 standard and CD44 variant 6 levels are not useful indicators of tumor burden and metastasis in patients with NSCLC. CD44 variant 6 expression might be associated with histological features of NSCLC.

Prognostic factors for patients with advanced non-small cell lung cancer: univariate and multivariate analyses including recursive partitioning and amalgamation.

In an attempt to determine the prognostic significance of pretreatment factors for patients with advanced non-small cell lung cancer (NSCLC), 24 pretreatment clinical variables were analyzed for 185 patients with NSCLC who underwent chemotherapy and/or radiotherapy between 1985 and 1994. Following univariate analysis, we applied two multivariate statistical techniques. In a Cox regression mode, independently significant factors influencing patient survival included performance status (PS), disease stage, hemoglobin level, and serum calcium level. Recursive partitioning and amalgamation (RPA) resulted in three distinct prognostic subgroups based on PS, stage, weight loss, and hemoglobin level. The best survival was observed for patients with a good PS and Stage III disease who had a hemoglobin level > 11 g/dl. The worst survival was observed for patients with a poor PS and presence of weight loss irrespective of stage. All other patients had an intermediate prognosis. Median survival times were 95.1 weeks, 17.1 weeks and 39.3 weeks, respectively (P < 0.00005). The results of our analyses show that three important prognostic subgroups could readily be discerned using RPA.

Measurement of serum p53 protein in patients with small cell lung cancer and results of its clinicopathological evaluation.

Serum p53 protein levels were measured in 36 patients with small cell lung cancer (SCLC) and 35 patients with benign lung diseases in order to evaluate the relationship of these levels to clinicopathological features of SCLC. Serum levels of p53 protein were measured by an enzyme-linked immunosorbent assay, p53 protein level was 23.92 +/- 6.78 pg/ml in patients with SCLC, and similar to that (17.47 +/- 2.86 pg/ml) in patients with benign lung diseases. By the clinical stage of SCLC, the mean level of p53 protein was 16.68 +/- 4.62 pg/ml in 21 patients with limited disease, and lower than that in 15 patients with extensive disease (34.05 +/- 14.84 pg/ml) (P = 0.23). The levels of p53 protein were not correlated with age, smoking index, or presence of cancer history for patients with SCLC. However, immunohistochemical examination disclosed a mild correlation between the expression of p53 protein by SCLC tumor and p53 protein serum level (r = 0.45, P = 0.02). Two patients with SCLC had an elevated serum level of p53 protein (> 2 S.D. above the mean for benign lung diseases). However, measurement of p53 protein serum level was not found to be clinically useful for detection of SCLC.