• Asian Pacific Journal of Cancer Prevention
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• v.15 no.10
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• pp.4147-4152
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• 2014

Standard therapy for advanced head and neck cancer consists of a combination of surgery and radiation. However, survival of this patient population has not improved during the past 20 years. Many different multimodality treatment schedules have been proposed, and chemotherapy is often used with the intent of organ preservation. The present study was intended to establish the efficacy of concomitant chemoradiation with a single agent carboplatin in advanced head and neck cancers.The objectives were to investigate the feasibility of concomitant administration of carboplatin, monitor acute toxicity during radiotherapy, and determine subacute side effects, such as wound healing following surgery after chemoradiotherapy. A prospective study was conducted wherein a total of 40 patients with stage III and IV squamous cell carcinomas of oral cavity, oropharynx, hypopharynx and larynx were enrolled. All patients were treated with external beam radiotherapy and weekly carboplatin area under curve (AUC of 5). Radiotherapy was given in single daily fractions of 1.8-2 grays (Gy) to a total dose of 66-72 Gy. Salvage surgery was performed for any residual or recurrent locoregional disease. Neck dissection was recommended for all patients with neck disease showing less than a complete response after chemoradiation. A total of 40 patients were enrolled of whom 32 were males and 8 were females. Highest incidence of cancer was seen in the 5th-6th decades of life with a median age of 47.7 years. Oropharyngeal tumours constituted a maximum of 21 patients followed by hypopharynx in 10, larynx in 7 and oral cavity in 2. 80% of the patients had a neck node on presentation of which 40% had N2-N3 nodal status. TNM staging revealed that 58% of patients were in stage III and 43% in stage IV. Evaluation of acute toxicity revealed that 50% had grade II mucositis, 25% grade III mucositis, 2.5% grade IV mucositis. 50% of patients had grade I skin reactions, 65% of patients had grade I thrombocytopenia, and 24% of patients had grade I anaemia. After completion of treatment 65% of patients had complete response at the primary and regional sites, and 35% of patients had a partial response of whom 23% underwent neck dissection and 5% of them underwent salvage surgery at the primary site. At the end of one year there were six deaths and four recurrences and 70% were free of disease. Concurrent chemoradiation with carboplatin provided good locoregional control for locally advanced head and neck cancers. This regimen, although toxic, is tolerable with appropriate supportive intervention. Primary site conservation is possible in many patients. Chemoradiotherapy appears to have an emerging role in the primary management of head and neck cancers.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.12
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• pp.5049-5053
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• 2014

Background: To investigate the expression of CD44v3 and vascular endothelial growth factor-C (VEGF-C) and their relationship with lymph node metastasis in squamous cell carcinomas (SCC) of the uterine cervix. Materials and Methods: Expression of CD44v3 and VEGF-C was analyzed in 109 cases of cervical SCC by immunohistochemistry (IHC). The relationship was analyzed between expression and the patient age, histological differentiation, formation of tumor emboli in lymphoid vessels, lymph node metastasis, FIGO staging, and TNM classification. Results: Expression rates for both CD44v3 and VEGF-C were 43.1% in cervical SCC. The cells with positive immunohistochemical staining of CD44v3 were distributed mainly around the keratin pearls in well differentiated carcinomas, but distributed diffusely in the moderately and poorly differentiated lesions. VEGF-C was found stained positively in most of the tumor cells. There were differences in expression between normal epithelium and atypical hyperplasia as well as carcinoma. Both CD44v3 and VEGF-C were found to be associated positively with lymph node metastasis and TNM classification (both p=0.000). Neither CD44v3 nor VEGF-C was found to be associated with patient age, histological differentiation, formation of tumor emboli in lymphoid vessels and FIGO staging. CD44v3 was found to be associated with VEGF-C positively (p=0.000). Conclusions: Abnormal expression of CD44v3 and VEGF-C is associated closely with the lymph node metastasis in cervical SCC, and these agents may cooperate in carcinogenesis and development of metastatic lesions.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.22 no.2
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• pp.164-173
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• 2000

The p16 protein is a cyclin dependent kinase inhibitor that inhibits cell cycle progression from $G_1$ phase to S phase in cell cycle. Many p16 gene mutations have been noted in many cancer-cell lines and in some primary cancers, and alterations of p16 gene function by DNA methylation have been noticed in various kinds of cancer tissues and cell-lines. There have been a large body of literature has accumulated indicating that abnormal patterns of DNA methylation (both hypomethylation and hypermethylation) occur in a wide variety of human neoplasma and that these aberrations of DNA methylation may play an important epigenetic role in the development and progression of neoplasia. DNA methylation is a part of the inheritable epigenetic system that influences expression or silencing of genes necessary for normal differentiation and proliferation. Gene activity may be silenced by methylation of up steream regulatory regions. Reactivation is associated with demethylation. Although evidence or a high incidence of p16 alterations in a variety of cell lines and primary tumors has been reported, that has been contested by other investigators. The precise mechanisms by which abnormal methylation might contribute to carcinogenesis are still not fully elucidated, but conceivably could involve the modulation of oncogene and other important regulatory gene expression, in addition to creating areas of genetic instability, thus predisposing to mutational events causing neoplasia. There have been many variable results of studies of head and neck squamous cell carcinoma(HNSCC). This investigation was studied on 13 primary HNSCC for p16 gene status by protein expression in immunohistochemistry, and DNA genetic/epigenetic analyzed to determine the incidence, the mechanisms, and the potential biological significance of its Inactivation. As methylation detection method of p16 gene, the methylation specific PCR(MSP) is sensitive and specific for methylation of any block of CpG sites in a CpG islands using bisulfite-modified DNA. The genomic DNA is modified by treatment with sodium bisulfate, which converts all unmethylated cytosines to uracil(thymidine). The primers designed for MSP were chosen for regions containing frequent cytosines (to distinguish unmodified from modified DNA), and CpG pairs near the 5' end of the primers (to provide maximal discrimination in the PCR between methylated and unmethylated DNA). The two strands of DNA are no longer complementary after bisulfite treatment, primers can be designed for either modified strand. In this study, 13 paraffin embedded block tissues were used, so the fragment of DNA to be amplified was intentionally small, to allow the assessment of methylation pattern in a limited region and to facilitate the application of this technique to samlples. In this 13 primary HNSCC tissues, there was no methylation of p16 promoter gene (detected by MSP and automatic sequencing). The p16 protein-specific immunohistochemical staining was performed on 13 paraffin embedded primary HNSCC tissue samples. Twelve cases among the 13 showed altered expression of p16 proteins (negative expression). In this study, The author suggested that low expression of p16 protein may play an important role in human HNSCC, and this study suggested that many kinds of genetic mechanisms including DNA methylation may play the role in carcinogenesis.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.30 no.1
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• pp.83-91
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• 2008

The goal of reconstruction following ablative therapy for intraoral cancer is the restoration of form and function to permit a return to activities of daily life. Traditional reconstruction includes split thickness skin grafts, myocutaneous flaps and, more recently, various free flaps. Free flaps provide higher level of functional recovery relative to that seen with other techniques but require the complexity of the technique and microvascular anastomosis and thus, extended surgical time and occasionally a second team for harvesting. The platysma myocutaneous cervical flap is a possible alternative for intraoral reconstruction. It is thin and pliable like the tissue provided by the radial forearm free flap. It can be harvested with enough tissue to close most head and neck ablative defects. There is virtually no donor site morbidity involved. This study evaluated 7 patients affected by intraoral squamous cell carcinoma (SCC). All patients underwent the resection of intraoral SCC with neck dissection and subsequent intraoral reconstruction with the superiorly based platysma myocutaneous cervical flap. Flap-related complications occurred in 3 patients. Adjuvant radiation therapy was performed in 3 patients. Average follow-up was 24.1 months after surgery, with a range of 8 to 42 months. All patients presented self assessment of discomfort associated with intraoral recipient sites and cervical donor sites. However, the neck function measured by two-inclinometer technique was within the normal range during relatively long term follow-up period. Our study concluded that superiorly based platysma myocutaneous cervical flap is good alternative to free flaps, especially for relatively smaller defects and for the defects appropriate for the rotation arc of the flap.

• Journal of Veterinary Clinics
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• v.26 no.1
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• pp.36-40
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• 2009

The purpose of this study was to determine the incidence and therapeutic outcomes of canine oral tumors in Korea. Medical records of dogs presented with oral tumor at the Veterinary Medical Teaching Hospital of Seoul National University from 2002 to 2007 were reviewed. The predominant breeds were Yorkshire terrier (n=14), miniature poodle (n=7), Shih Tzu (n=6), and maltese (n=4), in order. The mean age at onset was $10.0{\pm}3.8$ years. The most common tumor types included fibrous epulis (n=13), malignant melanoma (n=12), acanthomatous epulis (n=4), and squamous cell carcinoma (n=3). Surgical removal was performed in 29 cases; simple excision in 18 cases, partial mandibulectomy in 8 cases, and partial maxillectomy in 3 dogs. Outcomes of surgery were various according to the tumor types. Prognosis of dogs with fibrous epulis and acanthomatous epulis was good and that of dogs with malignant melanoma was poor.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.20 no.3
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• pp.263-268
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• 1998

Many myocutaneous flaps have been used for the reconstruction of intraoral defects caused by the excision of oral cancer. Among these myocutaneous flaps, cervical island flap has been introduced by Farr et al. Although different in detail, this flap was designed as the platysma myocutaneous flap by Futrell et al in the supraclavicular site. Since many authors applied this flap to cover intraoral defect, they discussed deeply the blood supply of this flap. To improve further flap survival, it was modified by Tashiro et al. This flap makes its vascularity highly reliable. The amount of tissue needed for reconstruction can be accurately planned. The surgical and reconstruction procedure can be performed simply, rapidly, and effectively. Oral functions including deglutition, speech, and denture fitting are not compromised. With it's minimal deformity, new donor fields is not necessory. Of course, we keep in mind that this flap has limitations in patients where much bulk of tissue defects is needed and more than 3000 rad radiation due to the metastasis of neck lymph node is exposed. In three patients with intraoral squamous cell carcinoma($T_{1-3}N_0M_0$), we performed induction chemotherapy with FP regimen including pepleomycin. Thereafter, we ablated oral cancer and peformed reconstruction of intraoral defects with cervical island flap designed by Tashiro et al. Due to these significant benefits and minimal limitations, we have found that this flap is adequate for reconstruction of most intraoral defects following cancer ablation.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.8
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• pp.3611-3615
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• 2012

Objective: The objective of this study was to establish the diagnostic accuracy, specificity and sensitivity of fine needle aspiration cytology(FNAC) for intra-oral tumors, comparing with histopathology as the gold standard. Materials and methods: Forty cases of FNA cytology from intraoral tumors was performed in AFID along with the demographic data and clinical information and then diagnosed at AFIP, Rawalpindi. Then the cytology results obtained per FNAC were compared with the histopathological biopsy results of the same lesions. The following variables were recorded for each patient: Age, gender, site of biopsy, diagnosis. The data were entered and analyzed using Open-epi version 2.0. Diagnostic accuracy, sensitivity, specificity, positive predictive value and negative predictive value were calculated. Cohen Kappa was further applied to compare the agreement between the biopsy and FNAC diagnoses. A p-value of < 0.05 was considered as statistically significant. Results: Among the total patients included in the study there were 24 males and 16 females, with a ratio of 1.5:1. Age of the patients ranged from 24 to 80 years with a mean of 52 years. A total of six sites were aspirated from the oral cavity with maximum (11) aspirates taken from alveolar ridge. The results of FNAC revealed that there were 32 malignant and 8 benign aspirates. Confirmation through histopathological analysis came for 31/32 malignant cases while one was falsely given positive for malignancy on FNAC. Among a total of 40 cases, 31(77%) cases diagnosed were found to be malignant and remaining 9(23%) were benign. The FNAC results revealed 32 malignant and 8 benign lesions. Histopathology of the subsequent surgically excised specimen showed malignant lesions in 31(77%) and benign in 9(23%) patients. As a whole, it was found that the absolute sensitivity for introral FNAC was 100% and specificity 89% with positive predictive value of 97% and negative predictive value of 100%. Conclusion: Cytological diagnosis was almost corroborative with final histopathological diagnosis in all cases, with very few exceptions, exhibiting high diagnostic accuracy.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.20 no.3
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• pp.246-249
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• 1998

With the recent progress of microsurgical techniques, radial forearm free flap has an established place in oral reconstruction. Providing thin, soft and pliable skin with a large and constant vascular pedicle, this flap is optimal for intraoral reconstruction. One of the disadvantages of the flap is donor site morbidity, therefore various methods can be used to reduce it. A male complained of palatal and retromolar area mass with ulceration, which was diagnosed as squamous cell carcinoma. He also complained of discomfort and mouth opening limitation, attributed to the location and characteristics of the mass. Because of mouth opening limitation, mandibular swing approach was performed to allow for the surgical approach to the mass. After the surgical excison of the lesion, the intraoral defect was successfully reconstructed with radial forearm free flap.

• The Korean Journal of Physiology and Pharmacology
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• v.21 no.2
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• pp.161-168
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• 2017

Understanding the crosstalk mechanisms between perivascular cells (PVCs) and cancer cells might be beneficial in preventing cancer development and metastasis. In this study, we investigated the paracrine influence of PVCs derived from human umbilical cords on the proliferation of lung adenocarcinoma epithelial cells (A549) and erythroleukemia cells (TF-$1{\alpha}$ and K562) in vitro using $Transwell^{(R)}$ co-culture systems. PVCs promoted the proliferation of A549 cells without inducing morphological changes, but had no effect on the proliferation of TF-$1{\alpha}$ and K562 cells. To identify the factors secreted from PVCs, conditioned media harvested from PVC cultures were analyzed by antibody arrays. We identified a set of cytokines, including persephin (PSPN), a neurotrophic factor, and a key regulator of oral squamous cell carcinoma progression. Supplementation with PSPN significantly increased the proliferation of A549 cells. These results suggested that PVCs produced a differential effect on the proliferation of cancer cells in a cell-type dependent manner. Further, secretome analyses of PVCs and the elucidation of the molecular mechanisms could facilitate the discovery of therapeutic target(s) for lung cancer.

• THE JOURNAL OF KOREAN ORIENTAL ONCOLOGY
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• v.2 no.1
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• pp.43-56
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• 1996

The sprig of Sojekbojungwhan(消積保中丸) has been used for curing as a traditional medicine without any experimental evidence to support the rational basis for their clinical use. This experiment was carried out to evaluate the possible therapeutic or antitumoral effects of Sojekbojungwhan extract against cancer, and to study some mechanisms responsible for its effect. The cytotoxic and antitumor effects were evaluated on human cell lines(A549, hep3B, Caki-1, Sarcoma 180) after esposure to Sojekbojungwhan extract using in ILS, colony forming efficiency and SRB assay which were regarded as a valuable method for cytotoxic and antitumor effects of unknown compound on tumor cell lines. The results obtained in this studies were as follows. 1. As a result of exposure to Sojekbojungwhan extract, the proliferation of A549, hep3B, Caki-1, good correlations were shown from the results of SRB assay and those of clogenetic assay. 2. The oral administration of Sojekbojungwhan extact showed significant effects of increase of MST(mean survival time) and ILS(increased life span) depending on the increasing concentration. 3. Against squamous cell carcinoma induced by MCA, Sojekbojungwhan decreased not only the frequency of tumor production but also the number and weight of tumors per tumor bearing mice(TBM). Sojekbojungwhan also significantly suppressed the development of 3LL cell-implanted tumors by frequency and their size, and some developed tumors were regressed by the continuous treatment of Sojekbojungwhan extract into TBM. 4. Sojekbojungwhan extract also increased NK cell activities. According to the above results, it could be suggested that Sojekbojungwhan extract has some antitumor effects.