CYR61/CCN1 Regulates dCK and CTGF and Causes Gemcitabine-resistant Phenotype in Pancreatic Ductal Adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) develops extrinsic- and intrinsic-resistant phenotypes to prevent chemotherapies from entering into the cells by promoting desmoplastic reactions (DR) and metabolic malfunctions of the drugs. It is well established that these responses are also associated with pancreatic cancer cells' gemcitabine resistance. However, the mechanism by which these resistant pathways function in the pancreatic cancer cells remains poorly understood.

The MAZ transcription factor is a downstream target of the oncoprotein Cyr61/CCN1 and promotes pancreatic cancer cell invasion via CRAF-ERK signaling.

Myc-associated zinc-finger protein (MAZ) is a transcription factor with dual roles in transcription initiation and termination. Deregulation of MAZ expression is associated with the progression of pancreatic ductal adenocarcinoma (PDAC). However, the mechanism of action of MAZ in PDAC progression is largely unknown.

Cancer of unknown primary site: improved patient management with molecular and immunohistochemical diagnosis.

Cancer of unknown primary site (CUP) is a common heterogeneous clinicopathologic syndrome, but investigations and publications regarding these patients are rare. For the last 20 years, empiric "broad-spectrum" chemotherapy has been the standard therapy for the majority of these patients. More recently, improved immunocytochemistry and advent of gene-expression profiling have provided the diagnostic tools necessary to accurately define the tissue of origin in most patients.

A phase I and pharmacokinetic study of oral lapatinib administered once or twice daily in patients with solid malignancies.

Purpose: This study determined the range of tolerable doses, clinical safety, pharmacokinetics, and preliminary evidence of clinical activity following once or twice daily administration of lapatinib in patients with solid malignancies.

Experimental Design: Cancer patients (n = 81) received oral doses of lapatinib ranging from 175 to 1,800 mg once daily or 500 to 900 mg twice daily. Clinical assessments of safety and antitumor activity were recorded and blood was sampled for pharmacokinetic assessments.

Recurrent laryngeal nerve monitoring during mediastinoscopy: predictors of injury.

Background: Recurrent nerve injuries occur during mediastinoscopy despite assiduous technique. We evaluated mediastinoscopy by monitoring laryngeal nerve stimulation during the surgery. These techniques utilize sensing electrodes on laryngeal masks to evaluate stimulus of the larynx, and are used to identify recurrent nerves during redo neck surgery.

Postoperative respiratory failure.

This analysis differentiates the causes of postoperative respiratory failure. Respiratory failure in thoracic patients is broken down into two distinct groups, aspiration and pneumonia, promoting actions to prevent respiratory failure. The goal is to develop different strategies to avoid postoperative respiratory failure using an active approach (what can be done in the management of patients undergoing lung resection to prevent problems) rather than passive approach (what patient factors caused problems after surgery).

Evolving role of irinotecan in small-cell lung cancer.

Irinotecan has recently been found to be one of the most active agents in the treatment of small-cell lung cancer (SCLC). Japanese investigators have led the way in the early investigation of irinotecan, and multiple studies are now ongoing in the United States. In a phase II trial conducted by the West Japan Thoracic Oncology Group, irinotecan was associated with a median survival of 13 months in patients with extensive-stage disease.

Recent updates on the role of chemotherapy in pancreatic cancer.

Single-agent gemcitabine remains the standard treatment for advanced pancreatic cancer. Recent phase III trials have failed to show improvements in survival using gemcitabine in combination with other chemotherapeutic agents, although the gemcitabine/oxaliplatin combination has shown some promise. The combination of gemcitabine with erlotinib was associated with a significant prolongation of survival.

Phase II trial of oral rubitecan in previously treated pancreatic cancer patients.

Background: Additional systemic treatments for locally advanced or metastatic pancreatic cancer are needed, as current treatment options produce only modest survival benefits. Rubitecan (Orathecin; Supergen Inc., Dublin, CA, http://www.

A phase II trial of preoperative concurrent radiation therapy and weekly paclitaxel/carboplatin for patients with locally advanced non-small-cell lung cancer.

This study was designed to evaluate the efficacy and toxicity of a novel preoperative combined-modality regimen in patients with locally advanced non-small-cell lung cancer (NSCLC). Patients with clinical stage IIB, IIIA, or IIIB NSCLC received preoperative combined-modality therapy with concurrent radiation therapy (RT) and weekly paclitaxel/carboplatin for 5 consecutive weeks. After this treatment, patients believed to have resectable disease by standard surgical criteria underwent thoracotomy.

Weekly combination chemotherapy with docetaxel and gemcitabine as first-line treatment for elderly patients and patients with poor performance status who have extensive-stage small cell lung carcinoma: a Minnie Pearl Cancer Research Network phase II trial.

Background: The goal of the current study was to evaluate the feasibility, toxicity, and efficacy of a novel combination of weekly docetaxel and gemcitabine for elderly patients and patients with poor performance status who had advanced-stage small cell lung carcinoma (SCLC).

Methods: Previously untreated patients with advanced-stage SCLC were eligible for the current clinical trial. In addition, patients were required to be age > 65 years or to have poor performance status (Eastern Cooperative Oncology Group 2).

Phase II trial of trastuzumab followed by weekly paclitaxel/carboplatin as first-line treatment for patients with metastatic breast cancer.

Purpose: To determine the response rate of trastuzumab as first-line therapy in patients with HER-2 overexpressing metastatic breast cancer. To assess the feasibility and toxicity of weekly paclitaxel/carboplatin with or without trastuzumab following initial treatment with trastuzumab.

Patients And Methods: Sixty-one patients received trastuzumab (8 mg/kg followed by 4 mg/kg/wk) for 8 weeks.

Gefitinib in the treatment of advanced, refractory non-small-cell lung cancer: results in 124 patients.

To evaluate the feasibility, toxicity, and efficacy of oral gefitinib (ZD1839, Iressa) in patients with refractory non-small-cell lung cancer (NSCLC) treated in a community-based setting. One hundred twenty-four patients with advanced, refractory NSCLC received treatment with gefitinib 250 mg orally each day. Ninety-six percent of patients had received >or= 1 previous chemotherapy regimens and 79% had received previous platinum and taxane therapy.

Combination treatment with weekly docetaxel and gemcitabine for advanced non-small-cell lung cancer in elderly patients and patients with poor performance status: results of a Minnie Pearl Cancer Research Network phase II trial.

The purpose of this study was to evaluate the feasibility, toxicity, and efficacy of the combination of weekly docetaxel and gemcitabine in patients with advanced non-small-cell lung cancer (NSCLC) who are either elderly or have poor performance status (PS). Patients with stage IIIB or IV NSCLC who had received no previous chemotherapy and were = 70 years of age were eligible for this clinical trial. Patients < 70 years of age were also eligible if they had poor PS or were considered poor candidates for standard platinum-based combination chemotherapy regimens.

Chemotherapy in metastatic and locally advanced non-small cell lung cancer.

The majority of patients with non-small cell lung cancer have locally advanced and metastatic disease at diagnosis. Combination platinum-based chemotherapy is the standard treatment for patients with advanced disease who have a performance status of 0-1. Chemotherapy is superior to supportive care alone in terms of survival, palliation of symptoms, and in many studies, improving quality of life.

First-line treatment with brief-duration chemotherapy plus rituximab in elderly patients with intermediate-grade non-Hodgkin's lymphoma: phase II trial.

This study was designed to evaluate the feasibility, toxicity, and efficacy of rituximab added to the VNCOP-B (etoposide/mitoxantrone/cyclophosphamide/vincristine/prednisone/bleomycin) combination regimen for the treatment of elderly patients with large B-cell lymphoma. Previously untreated patients > or = 65 years of age with stage II, III, or IV large B-cell non-Hodgkin's lymphoma were treated with a modified VNCOP-B regimen with weekly chemotherapy for 8 weeks. In addition, patients received rituximab 375 mg/m2 intravenously on weeks 1, 2, 3, 4, 6, and 8.

A phase I trial of weekly paclitaxel plus prolonged oral eniluracil/5-fluorouracil in patients with refractory malignancies.

Purpose: This phase I study was conducted to determine the dose-limiting toxicity (DLT), maximum-tolerated doses, and recommended phase II doses of the combination of weekly intravenous paclitaxel and oral eniluracil/5-fluorouracil (5-FU).

Patients And Methods: Patients received paclitaxel i.v.

Prospective randomized study of four novel chemotherapy regimens in patients with advanced nonsmall cell lung carcinoma: a minnie pearl cancer research network trial.

Background: The authors compared the toxicity, response rate, and progression free survival of four chemotherapy regimens for patients with advanced (Stage IIIB and IV) nonsmall cell lung carcinoma.

Methods: A total of 267 patients entered this randomized Phase II trial on one of four arms: paclitaxel, carboplatin, and gemcitabine (Arm A); paclitaxel, carboplatin, and vinorelbine (Arm B); paclitaxel and gemcitabine (Arm C); and gemcitabine and vinorelbine (Arm D). Patient characteristics were similar in all treatment arms.

Paclitaxel, carboplatin, and topotecan in the treatment of patients with small cell lung cancer: a phase II trial of the Minnie Pearl Cancer Research Network.

Background: The objective of this study was to evaluate the feasibility, toxicity, and efficacy of a novel three-drug regimen containing paclitaxel, carboplatin, and topotecan followed by oral etoposide in the first-line treatment of patients with small cell lung carcinoma.

Methods: One hundred five patients with previously untreated, limited stage or extensive stage small cell lung carcinoma were treated in this multicenter, community-based, Phase II trial. All patients received paclitaxel 135 mg/m(2) by 1-hour intravenous (i.

Phase I study of JM-216 (an oral platinum analogue) in combination with paclitaxel in patients with advanced malignancies.

This phase I study was conducted to determine the dose limiting toxicity, maximum tolerated doses, and recommended phase II doses of the combination of JM-216 and paclitaxel. Patients received paclitaxel intravenously over one hour on day 1 of each cycle. Oral JM-216 was administered on days 1-5 starting after the paclitaxel infusion.

Paclitaxel-based combination chemotherapy in advanced non-small cell lung cancer.

Paclitaxel has proven to be a useful drug for patients with advanced non-small cell lung cancer (NSCLC). Paclitaxel-based combination chemotherapy, particularly with carboplatin, has become a very popular combination in the US. This article will review the conclusions of several studies regarding paclitaxel-based chemotherapy.

Paclitaxel and carboplatin adjuvant therapy alone or with radiotherapy for resected nonsmall cell lung carcinoma: a feasibility study of the Minnie Pearl Cancer Research Network.

Background: The objective of this study was to determine the feasibility and toxicity of paclitaxel and carboplatin given in the adjuvant setting alone for patients with resected Stage IB disease and combined with radiotherapy for patients with resected Stages II and IIIA disease and selected patients with Stage IIIB and IV disease (Revised International System for Staging of Lung Cancer).

Methods: One hundred two patients with resected nonsmall cell lung carcinoma were treated in the postoperative period with 3 courses of paclitaxel 200 mg/m(2) intravenously (i.v.

Docetaxel (Taxotere) in combination with radiation therapy and the potential of weekly administration in elderly and/or poor performance status patients with advanced non-small cell lung cancer.

A randomized phase II trial conducted by the Cancer and Leukemia Group B in patients with unresectable non-small cell lung cancer showed that induction chemotherapy followed by concurrent radiotherapy and chemotherapy was feasible when cisplatin was administered together with either gemcitabine, vinorelbine, or paclitaxel. The dominant toxicity was esophagitis. Preliminary survival data are encouraging.

Monoclonal antibody therapy in lymphoid malignancies.

The concept of targeted therapy for patients with advanced cancer has intrigued researchers for many years. The lymphoid malignancies are particularly good candidates for this therapeutic approach, due to the identification of multiple lymphocyte-specific antigens. The recent introduction of rituximab marks the beginning of a new era in the treatment of lymphoid malignancies.

Docetaxel (Taxotere) in HER-2-positive patients and in combination with trastuzumab (Herceptin).

In addition to being an important indicator of poor prognosis, human epidermal growth factor receptor-2 (HER-2) status may help identify those patients in whom chemotherapy is the most appropriate choice of therapy. In several studies, including a trial of sequential neoadjuvant therapy in which certain patients received docetaxel (Taxotere; Rhône-Poulenc Rorer, Antony, France) following four courses of cyclophophamide 1000 mg/m2, doxorubicin 50 mg/m2, vincristine 1.5 mg/m2 on day one, and prednisone 40 mg by mouth for 5 days, HER-2 positivity predicted response (including pathologic response) to chemotherapy.