Oncologists and scientists in the field of head and neck cancer exchanged their research findings and clinical experiences in the Sino-USA Symposium on Head and Neck Cancer, which was held January 6-7, 2012 in Guangzhou, China. The symposium was jointly organized by Sun Yat-sen University Cancer Center (SYSUCC) and the University of Texas MD Anderson Cancer Center (MDACC). The Guangdong Provincial Anti-Cancer Association and the Chinese Journal of Cancer also helped in organizing the conference. Speakers were from China (SYSUCC, the Chinese University of Hong Kong, Tianjin Medical University Cancer Institute and Hospital, and Fudan University Shanghai Cancer Center) and the United States (MDACC). The presentations covered most kinds of head and neck cancers and included both basic and clinical research progress. In particular, NPC was discussed in depth. The symposium explored the reality that cancer is complex and numerous questions remain to be answered, even though there has already been an enormous effort into research. International exchanges of experience and in-depth cooperation are definitely needed to improve our capability of caring for cancer patients. In this article, we provide highlights of the presentations.
Carcinoma, Squamous Cell ; genetics ; Combined Modality Therapy ; Drug Delivery Systems ; Head and Neck Neoplasms ; drug therapy ; etiology ; genetics ; pathology ; surgery ; Humans ; Nasopharyngeal Neoplasms ; genetics ; pathology ; therapy ; Thyroid Neoplasms ; epidemiology

PURPOSE: KAI1 COOH-terminal interacting tetraspanin (KITENIN) has been found to act as a promoter of metastasis in murine models of colon cancer and squamous cell carcinoma (SCC). The suppression of tumor progression and metastasis of established colon cancer in mice was observed after intravenous delivery of small interfering RNA (siRNA) targeting KITENIN. The purpose of this study was to investigate the efficacy of gene therapy targeting KITENIN in human head and neck SCC. MATERIALS AND METHODS: SNU-1041, a well-established human hypopharyngeal SCC cell line, was used. KITENIN expression in SNU-1041 was measured by Western blot analysis. The cells were prepared, maintained in culture dishes with media, and divided into two groups: the si-KITENIN group and the scrambled group (control). The siRNA targeting KITENIN (si-KITENIN) and scrambled DNA were transfected into the SNU-1041 cells in each group. The effect of gene therapy was compared by in vitro experiments to evaluate invasion, migration, and proliferation. RESULTS: KITENIN was strongly expressed in the SNU-1041 cells, and the number of invaded cells was reduced more in the si-KITENIN group than in the scrambled group (p<0.001). The speed for the narrowing gap, made through adherent cells, was lower in the si-KITENIN group (p<0.001), and the number of viable proliferating cells was reduced in the si-KITENIN group compared to the scrambled group (p<0.001, the third day). KITENIN protein expression was no longer identified in the si-KITENIN group. CONCLUSION: Gene therapy using an anti-KITENIN strategy might be effective for head and neck squamous carcinoma.
Carcinoma, Squamous Cell/genetics/pathology/*therapy ; Carrier Proteins/*antagonists & inhibitors/genetics ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; *Gene Therapy ; Head and Neck Neoplasms/genetics/pathology/*therapy ; Humans ; Membrane Proteins/*antagonists & inhibitors/genetics ; *RNA, Small Interfering

OBJECTIVE: To study the effects of adenovirus-mediated tissue factor pathway inhibitor-2 gene on the invasion of laryngeal squamous cancer. METHOD: Ad-TFPI-2 was transfected into laryngeal squamous cancer (Hep-2) cell. Western-blot was used to test the TFPI-2 protein expression and Boyden Chamber experiment was used to examine the invasive ability of Hep-2 cells. Furthermore, the Ad-TFPI-2 infected Hep-2 cells were subcutaneously inoculated in nude mice and the tumor formation capability were observed. RESULT: Ad-TFPI-2 was identified correctly by endonuclease and sequencing and the virus titer was 2.8 x 10(13) PFU/L. In the Hep-2 cells of treated group, the TFPI-2 protein expression was increased while the invasive capability was descent. The tumor formation capability was also decreased in the treated group nude mouse model. CONCLUSION TFPI-2 recombinant adenovirus can effectively inhibit the invasive capability of laryngeal squamous cancer.
Adenoviridae ; genetics ; Animals ; Carcinoma, Squamous Cell ; pathology ; Cell Line, Tumor ; Genetic Therapy ; Genetic Vectors ; Glycoproteins ; genetics ; Humans ; Laryngeal Neoplasms ; pathology ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Transfection

OBJECTIVETo investigate the effects of survivin short hairpin RNA (shRNA) on survivin expression, cell apoptosis, and chemosensitivity of human tongue cancer cell Tca8113 to cisplatin.

METHODSSurvivin-directed shRNA plasmid vector was delivered into Tca8113 cells with lipofectamine(TM) 2000 reagent. Survivin expression was detected with the reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting. Flow cytometry was used to examine cell apoptosis, and the sensitivity to anticancer agents was evaluated by methyl thiazolyl tetrazolium (MTT) assay.

RESULTSAfter survivin shRNA vector transfection in Tca8113 cells, the expression of mRNA/protein declined significantly, and the apoptotic rate increased in time-dependent manner up to 37.9% at 48 hours. RNAi-mediated survivin reduction selectively inhibited growth and enhanced chemosensitivity of cisplatin but not of 5-fluorouracil.

CONCLUSIONSSurvivin shRNA could inhibit the expression of survivin mRNA and it's protein and enhance the chemosensitivity of cisplatin.

Apoptosis ; Carcinoma, Squamous Cell ; drug therapy ; genetics ; pathology ; Cell Line, Tumor ; Cisplatin ; pharmacology ; Drug Resistance, Neoplasm ; genetics ; Genetic Vectors ; Humans ; Liposomes ; Microtubule-Associated Proteins ; genetics ; metabolism ; RNA Interference ; RNA, Messenger ; genetics ; Tongue Neoplasms ; drug therapy ; genetics ; pathology ; Transfection

Lung squamous cell carcinoma (LSCC) accounts for approximately 30% of non-small cell lung cancer (NSCLC) cases and is the second most common histological type of lung cancer. Anaplastic lymphoma kinase (ALK)-positive NSCLC accounts for only 2%-5% of all NSCLC cases, and is almost exclusively detected in patients with lung adenocarcinoma. Thus, ALK testing is not routinely performed in the LSCC population, and the efficacy of such treatment for ALK-rearranged LSCC remains unknown. Echinoderm microtubule associated protein like 4 (EML4)-ALK (V1) and TP53 co-mutations were identified by next generation sequencing (NGS) in this patient with advanced LSCC. On December 3, 2020, Ensatinib was taken orally and the efficacy was evaluated as partial response (PR). The progression-free survival (PFS) was 19 months. When the disease progressed, the medication was changed to Loratinib. To our knowledge, Enshatinib created the longest PFS of ALK-mutant LSCC patients treated with targeted therapy since literature review. Herein, we described one case treated by Enshatinib involving a patient with both EML4-ALK and TP53 positive LSCC, and the relevant literatures were reviewed for discussing the treatment of this rare disease.
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Humans ; Carcinoma, Non-Small-Cell Lung/drug therapy* ; Lung Neoplasms/pathology* ; Anaplastic Lymphoma Kinase/metabolism* ; Carcinoma, Squamous Cell/genetics* ; Mutation ; Cytoskeletal Proteins/genetics* ; Lung/pathology* ; Oncogene Proteins, Fusion/genetics* ; Protein Kinase Inhibitors/therapeutic use* ; Tumor Suppressor Protein p53/genetics*

OBJECTIVE: To investigate the effect of tumor necrosis factor receptors II (TNFR II) in vivo transgene with topical injection of TNF alpha in inducing apoptosis and cell killing of laryngeal squamous carcinoma in nude mice animal model. METHOD: Laryngeal carcinoma implantation animal model was established on nude mice. In vivo gene transfection of TNFR II was carried out using liposome as a carrier. TNF alpha was topically injected into tumor. Goss measurement of tumor, flow cytometry, immunohistochemistry, tunel and transmission electron microscopy were conducted to observe the expression of TNFR II protein and the apoptosis of tumor cells, and the effects of tumor killing and growth inhibition was objectively evaluated. RESULT: Nude mice models bearing laryngeal carcinoma was established in 94.5% animals. After in vivo gene transfection, the expression of TNFR II protein reach the highest level at 48 hours, and remain in a substantially high level within 72 hours. Immunohistochemistry showed the expression of TNFR II is mainly on the cell membrane of the transfected tumor cells. Topical injection of 2000 U TNF alpha was most efficient in inducing tumor cell apoptosis, cell inhibition and cell killing. The tumor volume, weight, and tumor/body ratio in TNFR II transfected group were (1161.333 +/- 166.555) mm3, (1.100 +/- 0.832) g and 0.044 +/- 0.332, respectively, with a corresponding high level of tumor cell apoptosis rate (38.226 +/- 13.671) %, all of which were significantly higher than that in non-transfected group. Tunel and ultrastructural observations demonstrated apoptosis-related changes in the transfected tumor cells. CONCLUSION Up-regulation of TNFR II expression by in vivo gene transfection on tumor cells can remarkably enhance the tumor cell killing effect of topical injection of TNF-alpha. In vivo transgene of TNFR II in combination with topical injection of TNF alpha may become a effective gene therapy method in treating laryngeal cancer.
Animals ; Apoptosis ; drug effects ; Carcinoma, Squamous Cell ; pathology ; therapy ; Cell Line, Tumor ; Genetic Therapy ; methods ; Humans ; Laryngeal Neoplasms ; pathology ; therapy ; Mice ; Mice, Nude ; Receptors, Tumor Necrosis Factor, Type II ; genetics ; pharmacology ; Transfection ; Transgenes ; Tumor Necrosis Factor-alpha ; genetics ; pharmacology

OBJECTIVETo investigate the correlation between mutation in EGFR tyrosine kinase domain and tumor response as well as prognosis in advanced stage non-small cell lung cancer (NSCLC) treated with iressa.

METHODSFrom May 2002 to Feb. 2005, iressa was orally administered at a dose of 250 mg once daily for 106 advanced stage NSCLC patients until occurrence of disease progression or intolerable toxicity. Cancer tissue was obtained from these patients, and DNA was extracted for analysis of mutation in exon 18 to 24 of EGFR. Exon 18 to 24 of EGFR were amplified by nest PCR, sequenced and analyzed from both sense and antisence directions.

RESULTSPrimary NSCLC tissue specimens consisted of 25 frozen tissue blocks and 81 paraffin-embedded tumor tissue blocks from 106 consecutive NSCLC patients. Mutation was found to be more frequent in the adenocarcinoma than in the squamous cell carcinoma (35.9% vs 14.3%, P =0.033). Mutation was identified in 32 patients (30.2%). Response rate to iressa was 71.9% in the patients with EGFR mutation versus 13.5% in those without mutation (P <0.01). Compared with the patients without EGFR mutation, those with mutation had longer overall survival (median, 13.45 vs. 5.25 months; P<0.01) and median time to progression (median, 8.35 vs. 3.0 months; P <0.01).

CONCLUSIONEGFR mutation may be positively correlated with the response and survival in advanced stage Chinese NSCLC patient treated with iressa.

Adenocarcinoma ; drug therapy ; genetics ; pathology ; Adolescent ; Adult ; Aged ; Antineoplastic Agents ; therapeutic use ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; genetics ; pathology ; Carcinoma, Squamous Cell ; drug therapy ; genetics ; pathology ; Exons ; Female ; Follow-Up Studies ; Humans ; Kaplan-Meier Estimate ; Lung Neoplasms ; drug therapy ; genetics ; pathology ; Male ; Middle Aged ; Neoplasm Staging ; Point Mutation ; Prognosis ; Quinazolines ; therapeutic use ; Receptor, Epidermal Growth Factor ; genetics ; Sequence Deletion

OBJECTIVETo investigate the therapeutic effect and metabolism of 5-fluorocytosine (5-FC) in human tongue squamous carcinoma cells after treatment with adenovirus-mediated cytosine deaminase (AdCMVCD)/5-FC system.

METHODSHuman tongue squamous carcinoma cells (Tca8113 cell line) and its xenografts in BALB/c nude mice were treated with AdCMVCD/5-FC system. The killing effect in vitro and bystander effect were detected by microculture tetrazolium (MTT) assay. Tumor inhibition effect and histopathological changes were observed in vivo. High-performance liquid chromatography (HPLC) was performed to determine the metabolism of 5-FC in vitro and in vivo.

RESULTSAdCMVCD/5-FC system had strong killing effect and bystander effect on Tca8113 cells. Both condition media and cell extracts showed two peaks identified as 5-FC and 5-fluorouracil (5-FU) by HPLC and a time-dependent generation of 5-FU and concomitant time-dependent decreases of 5-FC. Compared to the control groups, mice treated with AdCMVCD/5-FC system demonstrated significant tumor regression (P < 0.001); the tumor doubling time prolonged and inhibition rate was 92.62%. There were substantial tumor necrotic areas and infiltrative lymphocytes around necrotic areas in the AdCMVCD/5-FC treated group under light microscope. There was a significantly low concentration of 5-FC and high concentration of 5-FU in tumor tissue, but only 5-FC was found in blood.

CONCLUSIONAdCMVCD/5-FC suicide gene system had significant in vitro and in vivo anti-tumor effect on human tongue squamous cell carcinoma due to convert 5-FC into 5-FU.

Adenoviridae ; genetics ; Animals ; Carcinoma, Squamous Cell ; pathology ; therapy ; Cytosine Deaminase ; Female ; Flucytosine ; metabolism ; therapeutic use ; Genetic Therapy ; Humans ; Mice ; Mice, Inbred BALB C ; Neoplasm Transplantation ; Nucleoside Deaminases ; genetics ; Tongue Neoplasms ; pathology ; therapy ; Transplantation, Heterologous ; Tumor Cells, Cultured

OBJECTIVETo investigate gene mutations of epidermal growth factor receptor (EGFR) and K-ras in Chinese patients with non-small cell lung cancer (NSCLC) and its clinicopathological significance, and to analyze the correlation between these mutations and tumor response to erlotinib treatment.

METHODSMutations of exons 18, 19, 20 and 21 of the EGFR and codons 12, 13 of the K-ras in 301 cases of NSCLC were detected by PCR-amplification and gene sequencing. The relationship between the mutations and clinicopathological characteristics of the 301 patients was analyzed.

RESULTSEGFR mutations were present in 32.9% (99/301) of the samples: 3 mutation in exon 18, 59 in exon 19, 2 in exon 20, and 35 in exon 21. Mutations of K-ras were present in 4.7% (14/301) of the samples: 13 in codon 12 and 1 in codon 13. EGFR mutations were never found in tumors with K-ras mutations, suggesting a mutually exclusive relationship. EGFR mutations were more common in adenocarcinomas, non-smokers and females. Seven out of 10 erlotinib-treated patients with disease control carried EGFR mutation.

CONCLUSIONThe frequency of EGFR mutation in Chinese NSCLC patients is higher than that in Westerners, but the frequency of K-ras mutation is quite opposite. Combined detection of EGFR gene and K-ras gene mutation may help clinicians to choose patients who may gain benefit from EGFR tyrosine kinase inhibitor (EGFR-TKI) treatment, and to predict their response to erlotinib treatment and prognosis.

Adenocarcinoma ; drug therapy ; genetics ; pathology ; Adult ; Aged ; Aged, 80 and over ; Asian Continental Ancestry Group ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; genetics ; pathology ; Carcinoma, Squamous Cell ; drug therapy ; genetics ; pathology ; Codon ; Erlotinib Hydrochloride ; Exons ; Female ; Genes, erbB-1 ; Genes, ras ; Humans ; Lung Neoplasms ; drug therapy ; genetics ; pathology ; Male ; Middle Aged ; Mutation ; Protein Kinase Inhibitors ; therapeutic use ; Proto-Oncogene Proteins ; genetics ; Proto-Oncogene Proteins p21(ras) ; Quinazolines ; therapeutic use ; Receptor, Epidermal Growth Factor ; genetics ; Sex Factors ; Smoking ; Young Adult ; ras Proteins ; genetics

Due to the advanced diagnostic technique and better understanding for multiple primary lung cancers (MPLC), the increasing incidence of MPLC has been reported. Very often, MPLC are misdiagnosed as metastasis because of lacking efficient molecular biomarkers for prediction and diagnosis. Studies on the molecular mechanism for tumorgenesis and progression of MPLC may therefore facilitate the discovery of biomarkers for disease diagnosis and prognosis, so that an individual and rational treatment can be achieved. We tried to further our understanding and improve the diagnostic skill for MPLC by reviewing the current status and the latest advancement of molecular markers related to MPLC.
Adenocarcinoma ; pathology ; Biomarkers, Tumor ; analysis ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; radiotherapy ; Carcinoma, Small Cell ; pathology ; Carcinoma, Squamous Cell ; pathology ; Chromosome Deletion ; DNA Damage ; Genes, Tumor Suppressor ; Humans ; Incidence ; Lung Neoplasms ; diagnosis ; epidemiology ; etiology ; genetics ; Neoplasms, Multiple Primary ; diagnosis ; epidemiology ; etiology ; genetics ; Smoking ; adverse effects