acyclovir and Lung-Neoplasms

Cigarette smoking is the leading cause of preventable death in the United States. Smoking adversely affects many organ systems, but especially the lung. Carcinoma of the lung and chronic obstructive pulmonary disease account for most smoking-associated respiratory morbidity and mortality, and their association with smoking is both well established and widely recognized. Cigarette smoking also is associated with differences in the incidence, severity, or natural history of a broad array of other respiratory illnesses, ranging from the common cold to pneumothorax, pulmonary hemorrhage, and various interstitial lung diseases. Interestingly, while the general effect of smoking on respiratory diseases is adverse, in the cases of sarcoidosis and hypersensitivity pneumonitis smoking may actually be associated with a decrease in the incidence of disease. In this article, the author briefly discusses some of the pulmonary and systemic effects of smoking that might mediate its effects on an array of lung diseases, then comprehensively reviews less common or less well-recognized smoking-affected lung diseases such as pulmonary infections, spontaneous pneumothorax, Goodpasture's syndrome, eosinophilic granuloma and other interstitial lung diseases, and pulmonary metastatic disease.

Topics: Acyclovir; Alveolitis, Extrinsic Allergic; Antiviral Agents; Arthritis, Rheumatoid; Asbestosis; Bronchiolitis; Chickenpox; Eosinophilic Granuloma; Humans; Lung Diseases; Lung Neoplasms; Pneumonia, Bacterial; Pneumonia, Viral; Pneumothorax; Pulmonary Fibrosis; Respiratory Tract Infections; Risk Factors; Smoking

We used a recombinant retrovirus as one of the potential vectors for human gene therapy to transfer a drug sensitivity gene into human lung cancer cells. The gene encoding the thymidine kinase (TK) of herpes simplex virus type 1 (HSV1) was used as the drug sensitivity gene. The antiherpes drugs acyclovir (ACV) and ganciclovir (GCV) were chosen to test the HSV1-TK activity transferred into the human lung cancer cell lines. The rationale for this approach was that ACV and GCV are nucleoside analogs specifically converted by HSV1-TK to a toxic form capable of inhibiting DNA synthesis or disrupting cellular DNA replication. The results obtained from our experiments demonstrate that the retroviral vector-mediated HSV1-TK gene transfer leads to ACV- and GCV-dependent cytotoxicity in human lung cancer cell lines, including both small-cell carcinoma and non-small-cell carcinoma. Although the gene transfer of HSV1-TK gene into tumor cells would be one model for gene therapy to control lung cancer, further investigations are necessary for the proper choice of the therapeutic gene and vector targeting such as tumor cell specific delivery of the gene or tumor cell specific expression of the transduced gene.

Topics: Acyclovir; Base Sequence; Cloning, Molecular; DNA, Recombinant; Ganciclovir; Gene Transfer Techniques; Genetic Therapy; Genetic Vectors; Humans; Lung Neoplasms; Molecular Sequence Data; Retroviridae; Simplexvirus; Thymidine Kinase; Transfection; Tumor Cells, Cultured

The biochemical mechanisms by which the antiviral drug Acyclovir (ACV) may induce anticancer effects even without detecting human herpesviruses (HHVs) are still poorly understood. Herein, we investigated for the first time how NCI-H1975 non-small cell lung cancer cells responded in vitro to ACV administration by exploring mitochondrial damage and apoptosis induction. We confirmed ACV ability to cause the inhibition of cancer cell growth even without detecting intracellular HHVs; the drug also significantly inhibited the colony formation capacity of NCI-H1975 cells. Cell cycle analysis revealed an increase of the sub-G1 hypodiploid peak after ACV treatment; the activation of caspase-3 and the presence of DNA laddering sustained the capacity of the drug to induce apoptotic cell death. Regarding mitochondrial toxicity, a reduction of mitochondrial membrane potential, altered mitochondrial size and shape, and mtDNA damage were found after ACV administration. Furthermore, an increment of intracellular reactive oxygen species levels as well as the upregulation of NudT3 involved in DNA repair mechanisms were observed. Altogether, these findings suggest that mitochondria may be possible initial targets and/or sites of ACV cytotoxicity within cancer cells in the absence of intracellular HHVs.

Topics: Acyclovir; Antineoplastic Agents; Apoptosis; Carcinoma, Non-Small-Cell Lung; Cell Line, Tumor; Cell Proliferation; DNA Damage; DNA, Mitochondrial; Humans; Lung Neoplasms; Membrane Potential, Mitochondrial; Mitochondria; Reactive Oxygen Species

Topics: Acyclovir; Aged; Antiviral Agents; Breast Neoplasms; Diagnosis, Differential; Exanthema; Facial Dermatoses; Female; Forehead; Herpes Zoster; Humans; Immunocompromised Host; Lung Neoplasms; Neoplasms, Multiple Primary

Topics: Acyclovir; Aged; Anti-Bacterial Agents; Anti-Inflammatory Agents; Anti-N-Methyl-D-Aspartate Receptor Encephalitis; Antimetabolites; Fatal Outcome; Humans; Lung Neoplasms; Male; Mental Disorders; Meropenem; Methylprednisolone; Movement Disorders; Small Cell Lung Carcinoma; Thienamycins

Topics: Acyclovir; Afatinib; Aged; Antineoplastic Agents; Antiviral Agents; Carcinoma, Non-Small-Cell Lung; Cystitis; ErbB Receptors; Esophagitis; Hematuria; Herpes Simplex; Humans; Intestinal Perforation; Lung Neoplasms; Male; Molecular Targeted Therapy; Neoplasm Proteins; Peritonitis; Protein Kinase Inhibitors; Quinazolines; Valacyclovir; Valine; Viremia; Virus Activation

Topics: Acyclovir; Antiviral Agents; Carcinoma, Non-Small-Cell Lung; Endoscopy, Gastrointestinal; Esophagitis; Herpes Simplex; Herpes Zoster; Humans; Immunocompromised Host; Lung Neoplasms; Male; Middle Aged

Over a 6-month period, 6 of 54 postthoracotomy patients developed pneumonia and respiratory failure. Pneumonia was secondary to herpes simplex virus type 1 in 3 of the 6 patients. Diagnostic efforts including bronchoscopy with bronchial washing, viral cultures, and cytologic examination permitted early diagnosis and successful treatment with acyclovir. A high index of suspicion for herpes simplex pneumonia must be maintained in critically ill patients with undiagnosed pneumonia.

Topics: Acyclovir; Aged; Female; Herpes Simplex; Herpesvirus 1, Human; Humans; Lung; Lung Neoplasms; Male; Middle Aged; Pneumonia, Viral; Postoperative Complications; Radiography; Thoracic Neoplasms; Thoracotomy

The most common causes of acute viral infections of the eye for which there are no effective antiviral drugs are the adenoviruses. Until recently, pathogenesis studies and antiviral drug testing for adenovirus-induced ocular disease were not practical because no animal model was available. However, new animal models for human adenovirus-induced ocular and respiratory infections have now made such studies possible. We assessed the in vitro and in vivo activity of ganciclovir against a genetically defined adenovirus (Ad5 wt 300) known to cause severe ocular disease. The 50% inhibitory dose (ID50) values were determined by plaque reduction assays in human cells. The ID50 values of 47 and 604 microM were determined for ganciclovir and acyclovir, respectively, against Ad5, and 26 and 152 microM, respectively against Ad8. Cotton rats were inoculated bilaterally with 10(5) plaque-forming units per eye and treated topically with ganciclovir (3%, 1%, or 0.3%) or placebo for 21 days. All inoculated eyes were culture positive on days 1-3 with increased infectivity titers, regardless of treatment. However, the incidence, duration, and titer of virus shed in eyes treated with 3% ganciclovir was reduced, and the antiadenovirus enzyme-linked immunosorbent assay titers in serum were lower in these animals. Although these differences were not statistically significant, the observed trend suggested that the highest ganciclovir dose had a suppressive effect on some disease parameters.

Topics: Acyclovir; Adenovirus Infections, Human; Adenoviruses, Human; Animals; Antibodies, Viral; Carcinoma; Enzyme-Linked Immunosorbent Assay; Eye Infections, Viral; Ganciclovir; Humans; Keratoconjunctivitis, Infectious; Lethal Dose 50; Lung Neoplasms; Ophthalmic Solutions; Sigmodontinae; Tumor Cells, Cultured; Virus Shedding

Cyclopentenylcytosine (CPE-C, 2), a pyrimidine analogue of the fermentation derived carbocyclic nucleoside neplanocin A, has been synthesized from the optically active cyclopentenylamine 3b by two synthetic routes. CPE-C demonstrates significant antitumor activity against both the sensitive and ara-C resistant lines of L1210 leukemia in vivo. Multiple long term survivors are produced in both tumor models. The compound also gives 100% growth inhibition of the solid human A549 lung and MX-1 mammary tumor xenografts grown in athymic mice. Good activity is also observed against a third human tumor xenograft model, metastatic LOX melanoma. CPE-C has significant activity against both DNA and RNA viruses in vitro. Potent activity is observed against HSV-1 (TK+ and TK-), HSV-2, vaccinia, cytomegalovirus, and varicella-zoster virus. Good activity is also found against a strain of influenza virus (Hong Kong flu), vesicular stomatitis virus, Japanese encephalitis virus, and Punta Toro virus.

Topics: 3-Deazauridine; Animals; Antineoplastic Agents; Antiviral Agents; Chemical Phenomena; Chemistry; Cytidine; DNA Viruses; Humans; Leukemia L1210; Leukemia P388; Lung Neoplasms; Mammary Neoplasms, Experimental; Melanoma; Mice; Mice, Nude; Neoplasm Transplantation; Neoplasms, Experimental; Orthomyxoviridae; RNA Viruses; Sarcoma, Experimental; Viruses