Response to bortezomib (velcade) in a case of advanced bronchiolo-alveolar carcinoma (BAC). A case report

A 65-year-old male with 40-pack year smoking history presented with exertional dyspnea and was subsequently diagnosed with bronchiolo-alveolar carcinoma (BAC). He did not respond to first line therapy with geftinib, but he achieved disease stabilization with gemcitabine and carboplatin for 4 months before developing symptomatic worsening requiring oxygen supplementation. He responded dramatically to bortezomib with rapid symptom improvement. The follow-up computerized tomography revealed partial response that was maintained for 11 months. Based on observations like this and those seen in phase I studies with bortezomib, this agent is being studied now in patients with bronchio-alevolar cancer.     

Gefitinib in patients with chemo-sensitive and chemo-refractory relapsed small cell cancers: a Hoosier Oncology Group phase II trial

BACKGROUND: Gefitinib has demonstrated activity in patients with non-small cell lung cancer (NSCLC). Clinical trials have not demonstrated a relationship between response to gefitinib and over-expression of the epidermal growth factor receptor (EGFR). Although, EGFR is not over-expressed in small cell lung cancer (SCLC), we postulated that gefitinib might affect tumor growth through other mechanisms. Agents that are active in NSCLC usually are also effective in SCLC. METHODS: The primary objective was to assess the clinical control rate: complete response (CR) partial response (PR) and stable disease (SD > 90 days), of gefitinib in patients with chemo-resistant and chemo-sensitive small cell cancers. Eligibility criteria included pathologic proof of a neuroendocrine tumor, especially small cell cancer, Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-2, prior treatment with one or two prior chemotherapy regimens and adequate end-organ function. Patients received gefitinib, 250 mg p.o. daily until disease progression or intolerable side effects. RESULTS: From April 2003 to March 2004, 19 patients were enrolled. Small cell lung cancer accounted for 18 of the 19 patients and one patient had metastatic Merkel cell carcinoma. Twelve patients (63%) had chemo-sensitive disease, defined as progression greater than three months from completion of prior chemotherapy; 7 (37%) had chemo-refractory disease; 13 (68%) had one prior chemotherapy regimen. Other patient characteristics: mean age 64 years (range 52-79 years); ECOG PS 0/1/2 = 7/9/3, M:F = 9:10. Grade 3 toxicities included: fatigue in three patients (15.8%), pulmonary toxicities in three (15.8%) and one patient (5.3%) each with hyperglycemia or pain. Four patients had grade four toxicities: one patient (5.3%) with fatigue and three patients (15.8%) with dyspnea. There were no patients with grade 3 or 4 rash or diarrhea. Two patients had stable disease (<90 days) and 17 had progressive disease as their best response. This study was a two-stage design and because the continuing criterion for stage one was not met, stage 2 was not performed. Median time to progression (TTP) was 50 days (95% CI = 21-58 days). One year overall survival (OS) was 21% (95% CI = 6-45.6%). CONCLUSION: Although gefitinib has activity in select patients with NSCLC, this study failed to demonstrate benefit in patients with small cell lung cancer.     

Computational Modeling of Kinase Inhibitor Selectivity

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Curcumin-artemisinin combination therapy for malaria

Artemisinin and curcumin show an additive interaction in killing Plasmodium falciparum in culture. In vivo, 3 oral doses of curcumin following a single injection of alpha,beta-arteether to Plasmodium berghei-infected mice are able to prevent recrudescence due to alpha,beta-arteether monotherapy and ensure almost 100% survival of the animals.     

Healthcare resource utilization and associated cost analysis of the PROCLAIM study in patients with stage III non-small-cell lung cancer

Objective: To analyze patient-reported swallowing difficulties, healthcare resource utilization and associated costs during the PROCLAIM study.

Methods: Patients with stage III non-squamous non-small cell lung cancer received pemetrexed-cisplatin (PemCis) combined with concurrent thoracic radiotherapy followed by consolidation pemetrexed, or concurrent chemoradiotherapy with etoposide-cisplatin (EtoCis) followed by standard consolidation chemotherapy. Patient?-?reported swallowing function was measured using diaries. Resource utilization (hospitalizations, transfusions, concomitant medications) was compared between treatment arms using Fisher’s exact test and independent t-test. Medical resource use costs were analyzed using nonparametric Wilcoxon rank sum test.

Results: Patient-reported difficulty in swallowing function (diary score ≥4) was 33.8% in the PemCis arm and 29% in the EtoCis arm. Overall resource use, including hospitalizations, was similar between treatment arms; however, fewer patients in the PemCis arm received transfusions and selected concomitant medications. Concurrent phase analyses were consistent with the overall study. A significantly lower percentage of patients (31.1% vs. 40.8%) were hospitalized in the PemCis arm. Total costs were significantly higher in the PemCis arm. Other medical costs (excluding study treatment costs) during the concurrent phase were lower for patients in the PemCis arm, due to significantly lower hospitalization costs and lower use of concomitant medications. Subgroup analysis yielded similar results.

Conclusions: Patient-reported difficulty in swallowing post-baseline and resource utilization were consistent with previously reported safety outcomes. In the overall study, higher total costs for PemCis were driven by study drug cost. When adjusting for treatment duration, other monthly medical costs were favorable to PemCis. Patients on pemetrexed remained longer on therapy, suggesting better tolerability.

ClinicalTrials.gov identifier: NCT00686959.     

Role of Shigella infection in endometriosis: a novel hypothesis

Endometriosis is the presence of endometrial cells and stroma at ectopic sites outside the uterine cavity. The natural history of endometriosis is uncertain, its etiology unknown, the clinical presentation inconsistent, diagnosis difficult and the treatment poorly standardized. It causes significant morbidity due to pelvic pain and infertility among 15-25% of women during their reproductive age. The benign disease causes peritoneal inflammation, fibrosis, adhesions and ovarian cysts but displays features of malignancy, like neo-vascularization, local invasion and distant metastasis. Mechanical, hormonal, immunological, environmental and genetic factors have been implicated in its etiology but provide inconclusive explanations. Present study was carried out on ectopic and eutopic endometriotic tissue specimens collected during laproscopy/laprotomy from cases of endometriosis. mRNA was isolated from the tissues and converted to cDNA by RT and subsequently subjected to differential display Polymerase Chain Reaction using seven sets of arbitrary primers. A unique band was identified only in the ectopic endometriotic tissue, which was sequenced. BLAST search results revealed sequence homology to shigella bacterial DNA leading us to hypothesize that infection may be playing a role in the etiology of endometriosis. This is the first report implicating the role of bacterial infection in the etiology of endometriosis. Shigella is known to invade the mucosa of the colon through the feco-oral route causing Shigellosis. The pathogenesis of shigellosis involves inflammation, ulceration, haemorrhage, tissue destruction and fibrosis of the colonic mucosa resulting in abdominal pain and diarrhoea/dysentery, this is similar to the pathogenesis of endometriosis which also involves inflammation, haemorrhage, tissue destruction and fibrotic adhesions of the pelvic peritoneum resulting in abdominal pain and infertility. The non-motile shigella bacteria invade the deeper mucosal layers by travelling from cell to cell of colonic epithelium, reaching the lamina propria of the colonic mucosa. We propose that, by the same mechanism, the bacteria travel across the colon wall to reach the outer peritoneal surface of the colon, which is in close proximity to the posterior uterine surface in the Pouch of Douglas, the site which incidentally happens to be the commonest site of early endometriosis. Our hypothesis therefore proposes that shigella or shigella-like organisms may be the trigger for the initiation of immunological changes in the pelvic peritoneum causing endometriosis. Once the endometrial cells are implanted at ectopic sites they are sustained by hormones and angiogenic factors. Hence "Infection hypothesis" provides a novel explanation for the etiopathogenesis of endometriosis.     

Device closure of pulmonary arteriovenous malformation using Amplatzer vascular plug II in hereditary hemorrhagic telangiectasia

Pulmonary arteriovenous malformations (AVM) are very rare and carry the risk of cerebral thrombo-embolism, brain abscess or pulmonary hemorrhage. The Amplatzer vascular plug II (AVP II) is a new device, used for embolization of the pulmonary AVMs. We report a case of pulmonary AVM successfully managed by using AVP II in a patient with hereditary hemorrhagic telangiectasia (HHT).     

Biologically active Chitosan/ZnO/Acalypha indica leaf extract biocomposite: An investigation of antibacterial,cell proliferation and cell migration aptitude for wound healing application

A biocomposite composed of Chitosan (Cs), Zinc oxide (ZnO), Acalypha indica (AI) was fabricated by simple chemical precipitation method. The achieved biocomposite was characterized by Fourier Transmission Infrared spectroscopy (FT-IR), X-ray diffraction spectroscopy (XRD), Scanning electron microscope (SEM) with Energy dispersive X-ray analysis spectroscopy (EDAX) and Transmission electron microscope (TEM). The phytochemical constituents in the AI leaf extract were also studied by Gas chromatography mass spectrometer (GC-MS) analysis. The anti-inflammatory and antioxidant studies were studied using Diclofenac sodium and ascorbic acid as standard by Fetal bovine serum denaturation and (2,2-diphenyl-1-picryl-hydrazyl-hydrate) DPPH radical scavenging method. The effective bactericidal action of the composite was evaluated against both gram-negative, gram-positive bacteria such as Escherichia coli (E.coli) and Staphylococcus aureus (S.aureus). The hemolysis activity was studied using Triton x 100 as negative and Phosphate buffer solution (PBS) as positive control. The biocompatibility nature was evaluated by the MTT (3- (4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide) MTT assay and Fluorescence staining method using mouse fibroblast cells (L929). Additionally, the in-vitro wound healing potential was also assessed by scratch wound assay with L929 mouse fibroblast cells. Hence, these obtained results suggest that the Cs/ZnO/AI biocomposite can act as a suitable candidate in wound care applications.