Cordycepin, a metabolite of Cordyceps militaris, inhibits xenograft tumor growth of tongue squamous cell carcinoma in nude mice / 南方医科大学学报

OBJECTIVE@#To evaluate the inhibitory effect of cordycepin on oral cancer xenograft in nude mice and explore the underlying mechanisms.@*METHODS@#Sixteen BALB/c mice bearing subcutaneous human tongue squamous cell carcinoma (TSCC) TCA-8113 cell xenografts were randomized into model group and cordycepin treatment group for daily treatment with saline and cordycepin for 4 weeks. After the treatment, the tumor xenografts were dissected and weighed to assess the tumor inhibition rate. Histological changes in the heart, spleen, liver, kidney, and lung of the mice were evaluated with HE staining, and tumor cell apoptosis was examined using TUNEL staining; The expressions of Bax, Bcl-2, GRP78, CHOP, and caspase-12 in the xenografts were detected using RT-qPCR and Western blotting.@*RESULTS@#Cordycepin treatment resulted in a tumor inhibition rate of 56.09% in the nude mouse models, induced obvious changes in tumor cell morphology and significantly enhanced apoptotic death of the tumor cells without causing pathological changes in the vital organs. Cordycepin treatment also significantly reduced Bcl-2 expression (P < 0.05) and increased Bax, GRP78, CHOP, and caspase-12 expressions at both the RNA and protein levels in the tumor tissues.@*CONCLUSION@#Cordycepin treatment can induce apoptotic death of TCA-8113 cell xenografts in nude mice via the endogenous mitochondrial pathway and endoplasmic reticulum stress pathways.

Oral ulcers and sarcoid-like reaction in lymph nodes after cemiplimab therapy for locally advanced cutaneous squamous cell carcinoma: a case report

ABSTRACT Cemiplimab is a novel programmed death-1 inhibitor recently approved for advanced cutaneous squamous cell carcinoma. Immune-related adverse events derived from cemiplimab are similar to other anti-PD-1 drugs, including gastrointestinal and cutaneous toxicities. Oral immune-related adverse events were not reported with cemiplimab in previous studies; thus this case report warns of the fact that the oral cavity may be a site of immune-related adverse events during programmed death-1 block therapy and that this can lead to significant limitations when not properly treated. The present report describes the case of a patient with locally advanced cutaneous squamous cell carcinoma metastatic to cervical lymph nodes who developed dysphagia due to large and painful oral ulcers after a single dose of cemiplimab. The patient also exhibited a sarcoid-like reaction in mediastinal lymph nodes. No immune-related adverse events were found in any other organs. The oral lesions showed significant improvement after topical and short-course systemic corticosteroids, and low-level laser therapy was also performed in the oral lesions. The patient achieved a near-complete response and treatment was discontinued. This article discusses in detail the clinical outcomes and oral toxicity management of cemiplimab therapy for cutaneous squamous cell carcinoma.

Clinical Observation of Immunotherapy Efficacy and Adverse Effects in Chinese Patients with Lung Squamous Cell Carcinoma / 中国肺癌杂志

BACKGROUND@#Immune checkpoint inhibitors (ICIs) improved survival of partial patients with lung squamous cell carcinoma (LUSC). However, it was still insufficient of data in older patients. This study aimed to investigate the efficacy and toxicity of immunotherapy in patients with LUSC in Chinese population of real world.@*METHODS@#A total of 185 LUSC patients underwent pathological diagnosis were involved from January 2018 to January 2022. Patients were divided into elderly group (age ≥70 years) and younger group (age <70 years). The efficacy of mono-immunotherapy or combined with chemotherapy to chemotherapy in first-line treatment was compared. The expression of programmed cell death ligand 1 (PD-L1) and tumor mutational burden (TMB) were evaluated. Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 was used to evaluate the efficacy, and Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 was used to evaluate immune-related adverse. Kaplan-Meier and Log-rank test was performed. Cox regression was used in prognostic analysis.@*RESULTS@#Combined therapy acquired significantly higher overall response rate (ORR) compared with chemotherapy alone in elderly group (P<0.05), and also in younger group, despite the difference was not significant (P>0.05). The median progression-free survival (mPFS) and median overall survival (mOS) in elderly group were similar with younger group (P>0.05). Both combined group and immunology alone demonstrated prolonged mPFS in first-line compared with chemotherapy in elderly group. And combined group demonstrated significantly prolonged mPFS compared with chemotherapy in younger group (P<0.01). There was no difference of mOS between different regimes in two groups. Elderly LUSC patients had higher PD-L1 positive rate (≥1%) and similar TMB compared with younger group. There was no relationship between mPFS and mOS with the expression of PD-L1 and TMB. Immunology combined with chemotherapy demonstrated better mPFS compared to chemotherapy in first-line therapy with TMB-High (P<0.05), and inferior mPFS with TMB-Low despite the difference was not significant (P>0.05). Cox regression model demonstrated that clinical stage was an independent predictor and prognostic factor. The incidence of immune-related adverse was 58.0% (51/88) and grade 3 or above 25.0% (22/88). The most common grade 3 adverse events were rash, immune-associated pneumonia, and fatigue.@*CONCLUSIONS@#Immunology combined with chemotherapy increased ORR, mPFS and mOS of Chinese patients with LUSC in first-line therapy compared with chemotherapy. There was no difference of efficacy and adverse effects rate between elderly group and younger group. The adverse effects of immunology in elderly patients with LUSC were controllable.

A Case Report of AFP-producing Primary Lung Squamous Cell Carcinoma with Significant Therapeutic Effect / 中国肺癌杂志

BACKGROUND@#Primary lung squamous carcinoma that produces alpha-fetoprotein (AFP) is rare and only four related cases have been reported so far. The specific reasons for elevated serum level of AFP and effective treatment regimens for AFP-producing lung squamous carcinoma are not clear. This paper reports the diagnosis and treatment of AFP-producing lung squamous carcinoma so as to provide some references for similar cases in clinical practice.@*METHODS@#The diagnosis and treatment of an AFP-producing lung squamous carcinoma patient admitted to the Shandong Cancer Hospital on October 23, 2020 was retrospectively analyzed, and literatures were reviewed.@*RESULTS@#A 52-year-old male patient was diagnosed as T4N3M0 stage, IIIc right upper lobe lung squamous cell carcinoma with mediastinal lymph node metastasis and multiple metastases in the lung. The main tumor marker was abnormally increased serum AFP. After the rapid progression of two lines chemotherapy, the patient was given anlotinib combined with carrizumab as third-line treatment. The efficacy evaluation reached to partial response (PR) and stable disease (SD) after 2 and 4 cycles of treatment, respectively. The treatment regimen was replaced with albumin paclitaxel plus carrizumab due to gastrointestinal bleeding after the fifth cycle. The patient's condition was under continuous control.@*CONCLUSIONS@#The AFP-producing lung squamous carcinoma patient had a good response to anlotinib and immunotherapy in the case report, which may provide some guidances for the clinical practice and the research on AFP-producing lung squamous carcinoma.

Biological effects of formulation containing curcuminoids and Bidens Pilosa L. in oral carcinoma cell line

Abstract: FITOPROT, which contains curcuminoids and Bidens pilosa L. extract, is an innovative mucoadhesive formulation indicated for the topical treatment of chemoradiotherapy-induced oral mucositis (OM) in patients with advanced and visible oral squamous cell carcinoma. The formulation is used as a mouthwash directly on tumor tissue of patients with advanced neoplasms, without triggering cancer cell proliferation or tumor invasiveness. Thus, the aim of this study was to evaluate the biological effects of FITOPROT on an oral squamous cell carcinoma cell line (SCC-4). The viability of SCC-4 cells was assessed after exposure to FITOPROT using MTT reduction assay. The effects of the mucoadhesive formulation on cell cycle progression and cell death parameters were evaluated using flow cytometry. In addition, the inflammatory profile of the tumor cells was evaluated using the cytometric bead array (CBA) assay. FITOPROT promoted a concentration-dependent decrease in cell viability and cell cycle arrest at the G2/M phase (p < 0.05). Mitochondrial membrane potential was also altered after exposure to the formulation (p < 0.05), in parallel with a reduction in VEGF and IL-8 production (p = 0.01 and p = 0.05, respectively). In summary, the results indicate that FITOPROT reduces SCC-4 cell viability, promotes cell cycle arrest, modulates mitochondrial membrane potential, and exhibits antiangiogenic and anti-inflammatory properties, thus indicating its potential for topical use in patients with OM and visible tumors in the mouth.

Ocular surface findings in impression cytology after interferon a2b or mitomycin C in rabbits / Achados em citologia de impressão da superfície ocular após uso de interferon alfa-2b ou mitomicina C: estudo em coelho

ABSTRACT Objective: To describe ocular surface findings in impression cytology obtained from healthy rabbit conjunctiva treated with interferon alpha-2b eyedrop, and compare them to findings after use of mitomycin C 0.02%. Methods: An experimental study using a rabbit model was performed between September 2013 and October 2014 at the Faculdade de Medicina de Marília, Universidade Federal de São Paulo, Clínica de Olhos Moacir Cunha. Thirty New Zealand white rabbits were divided into 6 groups and received interferon alpha-2b or mitomycin C 0.02%. Impression cytology (IC) was performed prior to topical applications and at15, 30 and 60 days of use. The following variables were analyzed in impression cytology: goblet cells, cellularity, cell-to-cell adhesion, nucleus/cytoplasm ratio, nuclear chromatin, inflammatory cells keratinization, and cytomegaly. Results: The major findings in impression cytology after us of interferon alpha-2b included loss of goblet cells (50.8%), reduced cell-to-cell adhesion (26.2%), abnormal nucleus/cytoplasm ratio (20%) and reduced cellularity (15.4%). After use of mitomycin C 0.02%, the most common changes included loss of goblet cells (46.2%), abnormal nucleus/cytoplasm ratio (25.6%), less cell-to-cell adhesion (23.1%), and reduced cellularity (20.5%). There were no significant differences in any variable when comparing impression cytology after interferon alpha-2b and after mitomycin C 0.02%. Goblet cell loss was more pronounced at days 30 and 60, as compared to impression cytology at day 15 for both drugs. Conclusion: The loss of goblet cells, reduced cell-to-cell adhesion and cellularity, along with abnormal nucleus/cytoplasm ratio were the most common findings in impression cytology after use of interferon alpha-2b. These findings are similar to those described for use of mitomycin C 0.02%. ..

RESUMO Objetivo: Descrever os achados em citologia de impressão de conjuntiva sadia de coelho submetida ao uso de colírio de interferon alfa-2b e compará-los ao que foi encontrado após uso da mitomicina C 0,02%. Métodos: Estudo experimental realizado em modelo animal no período entre setembro de 2013 e outubro de 2014 nas dependências da Faculdade de Medicina de Marília, da Universidade Federal de São Paulo e da Clínica de Olhos Moacir Cunha. Trinta coelhos albinos da raça Nova Zelândia foram divididos em seis grupos e receberam interferon alfa-2b ou mitomicina C. A citologia de impressão foi realizada antes do início dos colírios e após 15, 30, 60 dias de seu uso. As seguintes variáveis foram analisadas na citologia de impressão: células caliciformes, celularidade, adesão intercelular, razão núcleo/citoplasma, cromatina, células inflamatórias, queratinização e citomegalia. Resultados: Os principais achados na citologia de impressão após o uso do interferon alfa-2b foram a redução de células caliciformes (50,8%), a diminuição da adesão intercelular (26,2%), a alteração da razão N/C (20%) e a redução da celularidade (15,4%). Após o uso da mitomicina C 0,02%, foram mais frequentes a redução das células caliciformes (46,2%), a alteração da razão N/C (25,6%), a adesão intercelular (23,1%) e a redução da celularidade (20,5%). Não houve diferença estatisticamente significante para nenhuma das variáveis estudas quando se compararam as citologias de impressão após interferon alfa-2b com as citologias de impressão após mitomicina C 0,02%. Independentemente da substância utilizada, as citologias colhidas 30 e 60 dias após início das drogas apresentaram maior redução de células caliciformes quando comparadas com as citologias de impressão colhidas após 15 dias. Conclusão: A redução das células caliciformes, a diminuição da adesão intercelular, a alteração da razão N/C e a diminuição da celularidade foram as alterações mais frequentes na citologia de impressão colhida após o uso de interferon alfa-2b. Os achados em citologias de impressão após o uso de interferon alfa-2b são semelhantes àqueles encontrados após o uso da mitomicina C 0,02%.

Effects of salinomycin on proliferation and apoptosis of oral squamous cell carcinoma / 北京大学学报(医学版)

OBJECTIVE@#To investigate the effects of salinomycin on the proliferation and apoptosis of oral squamous carcinoma cells and to further understand the mechanisms of these effects.@*METHODS@#The human oral squamous carcinoma cell line CAL-27 was cultured in different concentrations of salinomycin and cisplatin. After co-culture with 0, 1, 2, 4, 8, 16 and 32 μmol/L salinomycin or 0, 1.25, 2.5, 5, 10, 20, 40 and 80 μmol/L cisplatin for 24 hours and 48 hours, the proliferation of oral squamous carcinoma cells were detected by cell counting kit-8(CCK-8) assay. After being exposed to 0, 2, 4, 8 μmol/L salinomycin and 0, 5, 10, 20 μmol/L cisplatin for 48 hours, the cell cycle of oral squamous carcinoma cells was detected by flow cytometry assay, and Western blot analysis was performed to analyze the expressions of cysteine-containing aspartate-specific proteases-3(Caspase-3), cysteine-containing aspartate-specific proteases-9(Caspase-9), poly ADP-ribose polymerase (PARP), protein kinase B (Akt) and phosphorylated protein kinase B (p-Akt) protein in oral squamous carcinoma cells.@*RESULTS@#Both salinomycin and cisplatin significantly inhibited the proliferation of oral squamous cell carcinoma CAL-27 cells in a time- and dose-dependent manner. However, compared with the first-line chemotherapeutic drug cisplatin, salinomycin showed stronger anti-proliferation activity in oral squamous carcinoma cells than cisp-latin (P < 0.001). After being exposed to 8 μmol/L salinomycin, CAL-27 cells exhibited markedly higher proportion in quiescent/ first gap phases (40.40%±1.99% vs. 64.46%±0.90%, P < 0.05), and had a significantly lower proportion in synthesis phases and second gap / mitosis phases (24.32%±2.30% vs. 18.73%±0.61%, P < 0.05; 35.01%±1.24% vs. 16.54%±1.31%, P < 0.05) compared with the dimethyl sulfoxide control group; moreover cisplatin didn't show cell-cycle specific effect on CAL-27. Western blot proved that salinomycin could up-regulate the expressions of Caspase-3 and Caspase-9 protein in oral squamous cell carcinoma CAL-27 cells (P < 0.05). At the same time, the levels of PARP, Akt and p-Akt protein were down-regulated (P < 0.05).@*CONCLUSION@#Compared with cisplatin, salinomycin has a better inhibitory effect on the proliferation of oral squamous carcinoma cells and blocks the cell cycle process at the quiescent / first gap phase. At the same time, salinomycin could trigger apoptosis of oral squamous carcinoma cells and the mechanism is associated with the Akt/p-Akt signaling pathway.

Lopinavir and curcumin directly alters BAX/BCL2 and VEFG165b mRNA levels to suppress human squamous cervical carcinoma cell growth / Lopinavir y curcumina alteran directamente los niveles de ARNm de BAX/ BCL 2 y VEFG165 para suprimir el crecimiento de células de carcinoma cervical escamoso humano

Following the success of the highly active antiretroviral therapy, the potential of multidrug combination regimen for the management of cancer is intensely researched. The anticancer effects of curcumin on some human cell lines have been documented. Lopinavir is a FDA approved protease inhibitor with known apoptotic activities. Dysregulated apoptosis is important for the initiation of cancer while angiogenesis is required for cancer growth and development, this study therefore investigated the effects of the combination of lopinavir and curcumin on cell viability, apoptosis and the mRNA expression levels of key apoptotic and angiogenic genes; BAX, BCL2 and VEGF165b in two human cervical cell lines; human squamous cell carcinoma cells - uterine cervix (HCS-2) and transformed normal human cervical cells (NCE16IIA). The two human cervical cell lines were treated with physiologically relevant concentrations of the agents for 120 h following which BAX, BCL2 and VEGF165b mRNA expression were determined by Real Time qPCR. The Acridine Orange staining for the morphological evaluation of apoptotic cells was also performed. The combination of lopinavir and curcumin up-regulated pro-apoptotic BAX and antiangiogenic VEGF165b but down-regulated the mRNA levels of anti-apoptotic BCL2 mRNA in the human squamous cell carcinoma (HCS-2) cells only. The fold changes were statistically significant. Micrographs from Acridine Orange staining showed characteristic evidence of apoptosis in the human squamous cell carcinoma (HCS-2) cells only. The findings reported here suggest that the combination of curcumin and the FDA approved drug-lopinavir modulate the apoptotic and angiogenic pathway towards the inhibition of cervical cancer.

Tras el éxito de la terapia antirretroviral altamente activa, se investiga intensamente el potencial del régimen de combinación de múltiples fármacos para el tratamiento del cáncer. Se han documentado los efectos anticancerígenos de la curcumina en algunas líneas celulares humanas. Lopinavir es un inhibidor de proteasa aprobado por la FDA con actividades apoptóticas conocidas. La apoptosis disrregulada es importante para el inicio del cáncer, mientras que la angiogénesis es necesaria para el crecimiento y desarrollo del cáncer. Por lo tanto, este estudio investigó los efectos de la combinación de lopinavir y curcumina sobre la viabilidad celular, la apoptosis y los niveles de expresión del ARNm de genes apoptóticos y angiogénicos clave: BAX, BCL2 y VEGF165b en dos líneas celulares cervicales humanas; células de carcinoma de células escamosas humanas: cérvix uterino (HCS-2) y células cervicales humanas transformadas (NCE16IIA). Las dos líneas celulares cervicales humanas se trataron con concentraciones fisiológicamente relevantes de los agentes durante 120 horas, después de lo cual la expresión de ARNm de BAX, BCL2 y VEGF165b se determinó mediante qPCR en tiempo real. También se realizó la tinción con naranja de acridina para la evaluación morfológica de células apoptóticas. La combinación de lopinavir y curcumina reguló incrementando BAX proapoptósicos y VEGF165b antiangiogénicos, pero reguló a la baja los niveles de ARNm del BCL2 antiapoptótico en células de carcinoma de células escamosas humanas (HCS-2) únicamente. Los cambios en el pliegue fueron estadísticamente significativos. Las micrografías de la tinción con naranja de acridina mostraron evidencia característica de apoptosis solo en las células del carcinoma de células escamosas humanas (HCS-2). Los hallazgos reportados aquí sugieren que la combinación de curcumina y el fármaco aprobado por la FDA lopinavir modulan la vía apoptótica y angiogénica hacia la inhibición del cáncer cervical.

Isolation of dihydrobenzofuran derivatives from ethnomedicinal species Polygonum barbatum as anticancer compounds

BACKGROUND: Ethnomedicinally, the family Polygonaceae is famous for the management of cancer. Various species of this family have been reported with anticancer potentials. This study was designed to isolate anticancer compounds from ethnomedicinally important species Polygonum barbatum. METHODS: The column chromatography was used for the isolation of compounds from the solvent fraction of P. barbatum. The characterization of isolated compounds was performed by various spectroscopic techniques like UV, IR, mass spectrometry and 1D-2D NMR spectroscopy. Keeping in view the ethnomedicinal importance of the family, genus and species of P barbatum, the isolated compounds (1-3) were screened for anticancer potentials against oral cancer (CAL-27) and lungs cancer (NCI H460) cell lines using MTT assay. Active compound was further investigated for apoptosis by using morphological changes and flow cytometry analysis. In vivo anti-angiogenic study of the isolated compounds was also carried using chorioallantoic membrane assay. Docking studies were carried out to explore the mechanism of anticancer activity. RESULTS: Three dihydrobenzofuran derivatives (1-3) have been isolated from the ethyl acetate fraction of P. barbatum. The structures of isolated compounds were elucidated as methyl (2S,3S)-2-(3,4-dimethoxyphenyl)-4-((E)-3-ethoxy-3-oxoprop-1-en-1-yl)-7-methoxy-2,3-dihydrobenzo-furan-3-carboxylate (1), (E)-3-((2S,3S)-2-(3,4-dimethoxyphenyl)-7-methoxy-3-(methoxy carbonyl)-2,3-dihydrobenzofuran-4-yl)acrylic acid (2) and (2S,3 S)-4-((E)-2-carboxyvinyl)-2-(3,4-dimethoxyphenyl)-7-hydroxy-2,3-dihydrobenzofuran-3-carboxylic acid (3). The compound 1 was found to be more potent with IC50 of 48.52 ± 0.95 and 53.24 ± 1.49 against oral cancer cells as compared to standard drug (IC50 = 97.76 ± 3.44 µM). Both compound also inhibited lung cancer cells but at higher concentrations. Morphological and flow cytometry analysis further confirms that compound 1 induces apoptosis after 24 to 48 h treatment. In antiangiogenesis assay, compounds 1, 2 and 3 exhibited IC50 values of 8.2 ± 1.1,13.4 ± 1.1 and 57.7 ± 0.3 µM respectively. The docking studies revealed that the compounds under study have the potential to target the DNA and thymidylate synthase (TS). CONCLUSION: Based on its overwhelming potency against the tested cell lines and in angiogenesis assay, compound 1 can be further evaluated mechanistically and can be developed as anticancer drug candidate.

Fatores prognósticos de resposta à quimioterapia em tumores avançados do colo uterino: o papel da neoangiogênese / Prognostic factors for response to chemotherapy in advanced tumors of the uterine cervix: the role of neoangiogenesis

RESUMO Objetivo: analisar a expressão do Fator de Crescimento do Endotélio Vascular (VEGF), seu receptor (VEGFR-2), idade e tipo histológico de carcinomas avançados de colo uterino com relação à resposta clínica à quimioterapia neoadjuvante. Métodos: foram incluídas 40 pacientes com diagnóstico de carcinoma de colo uterino (IB2 e IVA), com biópsias prévias ao tratamento. Todas as pacientes foram submetidas à quimioterapia neoadjuvante e avaliadas quanto à resposta clínica e à expressão do VEGF. Considerou-se boa resposta clínica uma regressão tumoral total ou maior do que 50%. Resultados: em relação à resposta à quimioterapia, 18 pacientes (45%) apresentaram boa resposta e 22 (55%), má resposta. Quanto à expressão do VEGF, em 16 pacientes foi considerada positiva e em 24, negativa. Quando os casos foram analisados separadamente em relação à resposta à quimioterapia, somente a expressão positiva de VEGF foi associada à boa resposta clínica (p=0,0157). Conclusão: a expressão de VEGF mostrou ser isoladamente, um importante marcador de boa resposta ao tratamento quimioterápico neoadjuvante das pacientes com carcinoma avançado de colo uterino.

ABSTRACT Objective: to analyze the expression of Vascular Endothelial Growth Factor (VEGF), its receptor (VEGFR-2), age and histological type of advanced cervical carcinomas with respect to the clinical response to neoadjuvant chemotherapy. Methods: we studied 40 patients with cervical carcinoma (IB2 and IVA) diagnosed by biopsies prior to treatment. All patients underwent neoadjuvant chemotherapy and evaluation for clinical response and expression of VEGF. We considered a tumor regression greater than 50% as a good clinical response. Results: eighteen patients (45%) had good response to chemotherapy, and 22 (55%), poor response. VEGF expression was positive in 16 patients and negative in 24. When analyzed separately for response to chemotherapy, only the positive expression of VEGF was associated with good clinical response (p=0.0157). Conclusion: VEGF expression alone was an important marker of good response to neoadjuvant chemotherapy in patients with advanced carcinoma of the cervix.

Experience in intra-arterial chemotherapy using two protocols for the treatment of OSCC over two decades at the University Hospital Vienna

OBJECTIVES: This retrospective study performed a comprehensive analysis of the usage of intra-arterial chemotherapy (iaCh) for locally recurrent UICC stage IV oral squamous cell carcinoma (OSCC) over two decades at the Department of Cranio-Maxillofacial and Oral Surgery at the University Hospital Vienna to assess the utility of its future use. METHODS: Between 1994 and 2014, iaCh was indicated in 48 OSCC cases. In these, the two most frequent iaCh schemes, cisplatin/5-fluorouracil (Cis/5-FU) and methotrexate/bleomycin (MTX/Bleo), were chosen for further analysis. The effect on survival of two distinct intra-arterial protocols and their covariates were analyzed with the Kaplan-Meier method as well as univariate and multivariate Cox proportional hazard regression models. RESULTS: The mean follow-up period was 29.91 months. The two intra-arterial chemotherapy groups did not differ significantly in sample size, demographic data or therapeutic covariates. The Cis/5-FU iaCh regimen was associated with significantly better overall survival (median OS 2.6 years vs. 1.3 years; p=0.002) and had a beneficial effect on survival (HR=3.62, p=0.015). Side effects occurred at a frequency similar to that described in the literature for intravenous chemotherapy (ivCh). CONCLUSIONS: These results suggest a preference for administering Cis/5-FU for iaCh. Nevertheless, due to economic considerations in healthcare expenditures, there is no future for iaCh in the treatment of head and neck carcinomas because ivCh is known to be equivalent.

Adjuvant treatment or primary topical monotherapy for ocular surface squamous neoplasia: a systematic review / Tratamento adjuvante ou monoterapia tópica primária para a neoplasia de células escamosas de superfície ocular: uma revisão sistemática

ABSTRACT In this systematic review, we evaluated studies involving adjuvant and primary topical treatment for ocular surface squamous neoplasia (OSSN). The findings were: (i) adjuvant 5-fluorouracil (5-FU) reduces the risk of relapse after surgical excision with mild side effects [level Ib, grade of recommendation (GR) A]. (ii) Primary topical mitomycin (MMC) produces a high rate of complete response, low recurrence rate, and mild side effects (level Ib, GR A). (iii) Primary chemotherapy versus adjuvant chemotherapy produce similar rates of recurrence, with no significant difference (level IIb, GR B). (iv) Adjuvant 5-FU versus MMC showed no significant differences, with mild side effects in both groups and a better toxicity profile for MMC (level III, GR C). (v) Primary topical 5-FU versus MMC versus interferon (IFN) showed similar rates of tumor recurrence, mild side effects for all drugs, and more severe side effects in the 5-FU arm, followed successively by MMC and IFN (level III, GR C).

RESUMO Revisão sistemática envolvendo estudos sobre o tratamento adjuvante e tratamento tópico primário para a neoplasia escamosa da superfície ocular. Os resultados foram: (i) 5-fluorouracil adjuvante reduziu o risco de recidiva após a excisão cirúrgica com efeitos colaterais leves (nível Ib, Grau de recomendação (GR) A). (ii) Mitomicina tópica primária produziu uma alta taxa de resposta completa, baixa taxa de recorrência e efeitos colaterais leves (nível Ib, GR A). (iii) Quimioterapia primária versus adjuvante produz taxas semelhantes de recorrência (nível IIb, GR B). (iv) 5- 5-FU versus mitomicina adjuvante não mostrou diferenças significativas nas taxas de recorrencia, com efeitos coalterais leves em ambos os grupos e melhor perfil de toxicidade para mitomicina (nível III, GR C). (v) 5- 5-FU tópico primário versus mitomicina ou interferon (INF) apresentam taxa similar de recorrência, com efeito colateral leve, mas com maior incidencia no braço 5- 5-FU, seguido pela Mitomicina e IFN (nível III, GR C).

Cytotoxic effect of thiabendazole on hn5 head and neck squamous cell carcinoma cell line

Statement of the Problem: Evidence shows thiabendazole has the potential to inhibit angiogenesis in melanoma and fibrosarcoma; however, its effect on oral squamous cell carcinoma has not been previously studied

Purpose: This study sought to assess the cytotoxic effects of thiabendazole on HN5 head and neck squamous carcinoma cell line

Materials and Method: HN5 cell lines were exposed to different concentrations of thiabendazole [prepared from 99% pure powder] for 24, 48 and 72 hours. Cell viability was assessed by the methyl thiazol tetrazolium assay, and IC50 of thiabendazole was calculated. Cells were also exposed to different concentrations of thiabendazole for 48 hours to determine its effect on expression and transcription of vascular endo-thelial growth factor gene. Expression of vascular endothelial growth factor mRNA was assessed by real-time polymerase chain reaction. The vascular endothelial growth factor release was assessed by the enzyme-linked immunosorbent assay test

Results: In all concentrations of thiabendazole except for 200 and 550uM, cell viability was significantly different at different time points [p< 0.05]. At 48 and 72 hours, cell viability at all concentrations of thiabendazole [100-65OuM] significantly decreased compared to the control group [zero concentration]

In addition, cell viability significantly decreased with an increase in thiabendazole concentration. At 48 hours, expression of vascular endothelial growth factor mRNA was significantly lower in presence of 500uM thiabendazole compared to the control group [p< 0.001] and release of vascular endothelial growth factor was inhibited in a dose-dependent manner

Conclusion: Thiabendazole inhibited the proliferation of HN5 cells in a dose-dependent and time-dependent manner. It also inhibited the expression of vascular endothelial growth factor gene

Health-related quality of life of patients with squamous cell carcinoma: a comparison according to tumor location

Abstract: The aim of this study was to evaluate the health-related quality of life (QOL) of patients with squamous cell carcinoma (SCC) according to tumor location. The sample consisted of 27 patients with primary SCC in the oral cavity (n = 15), pharynx (n = 7), and larynx (n = 5) who were undergoing cancer treatment at the Cancer Hospital of Londrina, regardless of age, sex, clinical stage, and type of antineoplastic treatment. Health-related QOL was evaluated using the 30-item Cancer-Quality of Life Questionnaire (QLQ-C30), the 35-item Head and Neck Cancer-Quality of Life Questionnaire (QLQ-HN35), and the University of Washington Quality of Life Questionnaire (UW-QOL). These questionnaires were administered individually to each patient before ambulatory care. Sociodemographic data (age and sex) and clinical data (T stage, tumor location, and type of antineoplastic treatment) were collected from the patients' medical records. Scores were compared according to tumor location using the chi-squared test and one-way analysis of variance (p < 0.05). No score differed significantly according to tumor location. It can be concluded that the health-related QOL of patients with SCC was not influenced by tumor location.

Erythroplasia of Queyrat treated with topical 5-fluorouracil

Abstract We report a 33-year-old male patient diagnosed with erythroplasia of Queyrat. The patient had an erythematous and eroded lesion affecting more than 50% of the glans associated with bleeding and local pain. Despite previous indication of penectomy, he was successfully treated with topical 5-fluorouracil.

Tratamiento no quirúrgico en cáncer epidermoide de orofaringe avanzado: análisis de resultados oncológicos en función del subsitio tumoral y fraccionamiento de radioterapia / Nonsurgical treatment in advanced oropharyngeal squamous cell cancer

Objetivo: Reportar resultados de nuestro protocolo de radioquimioterapia concomitante exclusiva en el cáncer de orofaringe avanzado. Materiales y métodos: Estudio retrospectivo que incluyó 87 pacientes. Se realizó radioterapia concomitante con cisplatino semanal. Se aceptó la realización de fraccionamiento convencional (FC), hiperfraccionamiento (Hfx) o fraccionamiento acelerado tipo boost concomitante (FABC). Se revisó la sobrevida global (SG), sobrevida libre de enfermedad (SLE), sobrevida libre de recidiva local (SLRL) y regional (SLRR) según subsitio y fraccionamiento. Resultados: Ingresaron 87 pacientes. Mediana de seguimiento: 120 meses. El 53, 30 y 17% recibieron FC, FABC y Hfx respectivamente. La SG a 2, 5 y 10 años fue de un 73, 61 y 43% respectivamente. La SG a 5 años según subsitio anatómico fue: amígdala 74%, paladar blando 33%, base de lengua 33%, y pared faríngea posterior 33%. Al comparar la SG de amígdala versus otros subsitios se alcanza una diferencia estadísticamente significativa (p < 0,001). La mediana de SG para amígdala no fue alcanzada, mientras que en otros subsitios fue de 22 meses. La SLE fue diferente en los distintos subsitios, superior en amígdala y diferente entre los distintos fraccionamientos, a favor de Hfx, alcanzando diferencias significativas. Las mismas tendencias se demostraron en SLRL y SLRR. Observamos un 23% de segundos primarios, siendo el pulmón el sitio más frecuente. Conclusión: La radioterapia concomitante con cisplatino semanal es un tratamiento adecuado para el cáncer de orofaringe. Ofrece excelentes resultados en cáncer de amígdala, especialmente con fraccionamiento modificado. Para los otros subsitios nos parece recomendable explorar nuevas estrategias de tratamiento.

Objective: To report results of our concomitant radiochemotherapy protocol for advanced oropharyngeal cancer. Materials and methods: Retrospective study. Concomitant radiochemotherapy was performed with weekly cisplatin. Conventional fractionation (CF), hyperfractionation (Hfx) or accelerated fractionation with concomitant boost (FABC) were accepted. Overall survival (OS), Disease-free survival (RFS), Local relapse-free survival (LRFS) and Regional relapse-free survival (RRFS) were calculated, according subsite and radiotherapy fractionation. Results: We found 87 patients. Median follow-up: 120 months. 53%, 30% and 17% received FC, FABC, Hfx respectively. OS at 2, 5 and 10 years was 73%, 61% and 43% respectively. The 5-year OS was, by anatomic subsite: Tonsillar 74%, 33% soft palate, base of tongue 33%, and 33% for posterior pharyngeal wall. By comparing the OS in tonsil versus other subsites we found statistically significant difference in favor of tonsillar cancer (P < .001). Median OS for tonsillar cancer was not achieved, while in other subsites was 22 months. DFS was different in different subsites, better for amygdala and different among different fractionations, better for Hfx, reaching significant differences. The same trends were demonstrated in LRFS and RRFS. We observed a 23% of second cancers, being lung the most common site. Conclusion: Concomitant radiotherapy with weekly cisplatin is an appropriate treatment for oropharyngeal cancer. It provides excellent outcomes in tonsillar cancer, especially with modified fractionation and Hfx type. For other subsites it seems advisable to explore a new treatment approach.

Carcinoma espinocelular del oído externo con extensión parotídea: a propósito de un caso / Squamous cell carcinoma of the external ear with parotid extension: case report

El pabellón auricular y el conducto auditivo externo constituyen una región anatómica que puede ser asiento de múltiples patologías, entre ellas procesos inflamatorios, infecciosos y neoplásicos, tanto benignos como malignos. Con respecto a los tumores, los diversos tipos suelen presentarse con síntomas y signos similares y en general es difícil inferir la variedad histológica del tumor a través del examen físico, por lo cual es necesario el estudio histopatológico para determinar el diagnóstico. La mayoría de los tumores del oído externo son carcinomas; entre ellos se destacan el carcinoma basocelular, el más frecuente, y el carcinoma espinocelular. Menos frecuentemente se encuentran otros tipos de tumores como los melanomas, adenocarcinomas, carcinomas de glándulas ceruminosas, carcinomas mucoepidermoides, sarcomas, procesos linfoproliferativos, etc. Suelen ocurrir en la edad media y avanzada (50-70 años) y con mayor periodicidad en el sexo masculino. En el presente trabajo se describe un caso clínico de carcinoma espinocelular del oído externo, tratado exitosamente mediante cirugía y radioterapia, así como también se describen las características clínicas de esta enfermedad, con especial atención al compromiso del oído externo por ella.

The pinna and the ear canal are an anatomical region that can be affected by many diseases, including inflammatory, infectious and benign and malignant neoplastic processes. With regard to tumors, various types usually present with similar symptoms and usually is very difficult to know the histological type through physical examination, so histopathological examination is necessary in order to determine the diagnosis. Most tumors are carcinomas; they can be basal cell carcinoma (more frequently), or squamous carcinoma. Less frequently are other types of tumors such as melanomas, adenocarcinomas, ceruminous glands carcinomas, mucoepidermoid carcinomas, sarcomas, lymphoproliferative disorders, etc. They usually present in middle and advanced age people (50-70 years) and are more frequently in men. In this article we present a case of squamous cell carcinoma of the external ear with extention to parotid gland, successfully treated with surgery and radiotherapy, as well as we describe the clinical characteristics of this disease, with special attention to the compromise of the external ear. (AU)

Utilização de eletroquimioterapia para carcinoma de células escamosas tegumentar em felino / Employment of electrochemotherapy for cutaneous squamous cell carcinoma in cats

A eletroquimioterapia compreende a utilização conjunta de fármacos antineoplásicos e aplicação regional de pulsos elétricos (eletroporação), maximizando a concentração intracelular destes fármacos, assim propiciando maior ação citotóxica. A bleomicina, fármaco antimicrobiano dotado de propriedade antineoplásica, apresenta restrita penetrabilidade na membrana celular, dada a sua hidrossolubilidade. Todavia, uma vez administrada via intralesional ou intravenosa associada à eletroporação, demonstra citotoxicidade potencializada. Foram utilizados 21 felinos acometidos por carcinoma de células escamosas tegumentar. Padronizou-se o protocolo eletroquimioterápico empregando-se sulfato de bleomicina, pela via intravenosa, na dose de 15U/m2 de superfície corpórea. A eletroporação foi perfilada com eletrodo composto por agulhas, pulsos elétricos com tensão de 1000 V, em onda quadrada unipolar, com duração de 100 microsegundos, totalizando oito ciclos. Verificou-se remissão neoplásica integral em 21 felinos inclusos no estudo (100%). Inexistiram complicações e/ou efeitos adversos decorrentes do procedimento. O protocolo avaliado neste trabalho revelou-se exequível, eficaz e seguro na terapêutica antineoplásica de carcinoma de células escamosas tegumentar felino.

Electrochemotherapy is characterized as a protocol which combines the use of antineoplastic agents and localized application of electric pulses (electroporation) to improve the intracellular concentration of these agents, increasing its cytotoxic action. Bleomycin, an antibiotic agent with antineoplastic properties, is a hydrophilic molecule, having a restricted transport through the cellular membrane. However, when it is administered intralesionally or intravenously and associated to electroporation, its cytotoxicity is maximized. There were utilized 21 cats affected by cutaneous squamous cell carcinoma. The electrochemotherapy protocol was standardized using intravenous bleomycin sulfate at a dose of 15U/m2 body surface area. Electroporation was performed using an electrode composed of needles and electric pulses with 1000 V voltage, in unipolar square wave and 100 microseconds duration, totalizing eight cycles. There was complete neoplastic remission in 21 cats (100%). There were no complications or side effects associated with the procedure. The protocol studied in this work showed to be feasible, effective and safe for antineoplastic therapy in feline cutaneous squamous cell carcinoma.

Details of recurrence sites after definitive radiation therapy for cervical cancer / 부인종양

OBJECTIVE: This is a retrospective study aimed at clarifying the details of recurrence patterns and sites in patients with cervical cancer treated with definitive radiation therapy (RT). METHODS: Data were analyzed from consecutive patients, admitted to the University of Tokyo Hospital (Tokyo, Japan) between 2001 and 2013, who had received definitive RT, with or without chemotherapy, for International Federation of Gynecology and Obstetrics stages IB-IVA cervical cancer. RESULTS: One hundred and thirty-seven patients formed the patient cohort. The median follow-up period for surviving patients was 57.0 months. A complete response was achieved in 121 patients (88%). Of these, 36 (30%) developed a cancer recurrence during follow-up. The first sites of recurrence were located in intra-RT fields in nine, outside RT fields in 20, and both in seven patients. In the intra-RT field group, all patients showed a local recurrence, while no one experienced an isolated pelvic lymph node (PLN) recurrence. In the outside RT field group, the most frequent site of recurrence was lung (60%), and three-quarters of patients were free from intra-RT field recurrence until the last follow-up. Of the entire cohort, including 48 PLN-positive patients, only seven patients (5.1%) developed PLN persistence or recurrence, all in the common iliac, internal iliac, and/or obturator nodes, and all with another synchronous relapse. CONCLUSION: Local disease was a major type of intra-RT field recurrence, while PLN control was favorable even in initially PLN-positive patients. The predominance of outside RT field recurrence alone highlights issues concerning distant control, including the intensity enhancement of systematic therapy.

Complete pathologic response as a prognostic factor for squamous cell carcinoma of the oropharynx post-chemoradiotherapy / Resposta patológica completa como fator prognóstico no carcinoma espinocelular de orofaringe após quimiorradioterapia

ABSTRACT INTRODUCTION: Chemoradiotherapy for squamous cell carcinoma of the oropharynx (SCCO) provides good results for locoregional disease control, with high rates of complete clinical and pathologic responses, mainly in the neck. OBJECTIVE: To determine whether complete pathologic response after chemoradiotherapy is related to the prognosis of patients with SCCO. METHODS: Data were prospectively extracted from clinical records of N2 and N3 SCCO patients submitted to a planned neck dissection after chemoradiotherapy. RESULTS: A total of 19 patients were evaluated. Half of patients obtained complete pathologic response in the neck. Distant or locoregional recurrence occurred in approximately 42% of patients, and 26% died. Statistical analysis showed an association between complete pathologic response and lower disease recurrence rate (77.8% vs. 20.8%; p = 0.017) and greater overall survival (88.9% vs. 23.3%;p = 0.049). CONCLUSION: The presence of a complete pathologic response after chemoradiotherapy positively influences the prognosis of patients with SCCO.

RESUMO Introdução: O tratamento baseado em quimirradioterapia do Carcinoma Espinocelular de Orofaringe (CECOF) apresenta bons resultados no controle locorregional da doença com boas taxas de resposta clínica e patológica completas especialmente no pescoço. Objetivo: Determinar se a resposta patológica completa após quimiorradioterapia estárelacionada aos prognósticos dos pacientes com CECOF. Método: Os dados foram obtidos de maneira prospectiva da revisão de prontuários de pacientes com CECOF N2 e N3 submetidos a esvaziamento cervical planejado após quimiorradioterapia. Resultados: Um total de 19 pacientes foram avaliados. Metade dos indivíduos apresentou resposta patológica completa no pescoço. Recidiva à distância ou locorregional ocorreu em aproximadamente 42% dos pacientes e 26% deles morreram. A análise estatística demonstrou uma associação entre resposta patológica completa e menor taxa de recidiva (77,8% vs.20,8%; p = 0,017) e maior sobrevivência global (88,9% vs.23,3%; p = 0,049). Conclusão: A presença de resposta patológica completa após quimiorradioterapia influencia positivamente no prognóstico de pacientes com carcinoma espinocelular de orofaringe.