Oral hyperpigmentation as an initial clinical aspect of hand foot syndrome

Abstract Hand-foot syndrome (HFS) is a common adverse effect of anticancer therapy. It is known to cause dermatological symptoms including acral erythema and dysesthesia of the palms and soles of the feet, swelling, pain, itching, and scaling. Some drugs, like capecitabine, are known to trigger this condition. However, pigmentation of the oral mucosa is a rare adverse effect. This study aims to report a case of oral mucosa hyperpigmentation caused by capecitabine therapy before the clinical diagnosis of HFS. A 58-year-old female, diagnosed with invasive breast duct carcinoma, had the central nervous system, liver, skin, and lung metastasis, using capecitabine every day for 14 cycles. Oral examination revealed multifocal black macules on the hard palate, bilateral buccal mucosa, gingival mucosa, and dorsum of the tongue. The clinical hypothesis was oral mucosa hyperpigmentation by capecitabine use and only periodic follow-up was necessary. Hyperpigmentation of oral mucosa by capecitabine is a rare consequence of neoplastic therapy and your association with HFS is unclear, and poorly reported. The report of these events is important to alert oncology health teams about the individual tolerance to capecitabine therapy.

Resumo A síndrome mão-pé (SMP) é um efeito adverso comum da terapia anticâncer. Sabe-se que causa sintomas dermatológicos, incluindo eritema acral e disestesia das palmas das mãos e solas dos pés, inchaço, dor, coceira e descamação. Alguns medicamentos como a capecitabina são conhecidos por desencadear essa condição. No entanto, a pigmentação da mucosa oral é um efeito adverso raro. Este trabalho tem como objetivo relatar um caso de hiperpigmentação da mucosa oral causada pela terapia com capecitabina antes do diagnóstico clínico de SMP. Mulher de 58 anos, com diagnóstico de carcinoma invasivo de ducto mamário, apresentou metástase no sistema nervoso central, fígado, pele e pulmão, em uso de capecitabina todos os dias por 14 ciclos. O exame oral revelou máculas negras multifocais no palato duro, mucosa bucal bilateral, mucosa gengival e dorso de língua. A hipótese clínica foi de hiperpigmentação da mucosa oral pelo uso de capecitabina e apenas o acompanhamento periódico foi necessário. A hiperpigmentação da mucosa oral pela capecitabina é uma consequência rara da terapia neoplásica e sua associação com SMP não é clara e pouco relatada. O relato desses eventos é importante para alertar as equipes de saúde oncológica sobre a tolerância individual à terapia com capecitabina.

Research progress of exosomes based targeted delivery of antitumor drugs / 药学学报

Exosomes are one of the most important ways of cell-to-cell communication in living lives. They are involved in major physiological and pathological processes, including drug resistance, infection propagation, cancer development and cardiovascular diseases. The biological functions of exosomes made it possess characteristics of low immunogenicity, high delivery efficiency, ability to cross multiple biological barriers and targeting capacity, which also encourage people to try to use it as a drug carrier to overcome the disadvantages of poor stability, low solubility, low bioavailability and high toxicity of some drugs. In this paper, the latest progress of exosomes in the delivery of antitumor drugs, including small chemotherapeutic drugs, biological macromolecules and nucleic acid drugs, is reviewed. In addition, the isolation, drug loading, and modification method and the application prospect of exosomes are also discussed.

Inhibitory effect of LZJ541, a novel small molecule inhibitor of STAT3, on the proliferation of hepatocellular carcinoma cells / 药学学报

Signal transducer and activator of transcription 3 (STAT3) is an important regulatory factor of cell proliferation and metastasis, involved in the occurrence and development of a variety of malignant tumors, and it is one of the hot spots in the research of targeted anti-tumor drugs. Our group screened a novel benzobis (imidazole) structure small molecule compound LZJ541 through the screening model of Janus kinase (JAK)/STAT3 pathway inhibitors, which has definite STAT3 inhibitory activity. We examined the effect of LZJ541 on the proliferation of HepG2 and PC-3 cells by MTT assay in vitro, detected the effect of LZJ541 on the expression of STAT3-related proteins in HepG2 cells by Western blot, and measured the effect of LZJ541 on the apoptosis and cell cycle arrest of HepG2 cells via flow cytometry. The results indicated that LZJ541 significantly inhibited the activation of STAT3 signaling pathway and restrained the proliferation of HepG2 cells. Its half maximal inhibitory concentration (IC50) was 13.8 μmol·L-1, which was much lower than that of PC-3 cells (with low STAT3 expression, IC50: 41.99 μmol·L-1), LZJ541 can also inhibit the phosphorylation of STAT3 in HepG2 cells, thereby inducing apoptosis and cycle arrest and then exerting anti-tumor effects. In conclusion, LZJ541 has a certain anti-tumor effect in vitro, which provides an experimental basis for the development of new STAT3-targeted anti-tumor drugs around this kind of compounds.

Research progress on STAT protein inhibitors in the treatment of lymphoma / 药学学报

The abnormal activation and mutation of signal transducer and activator transcription (STAT) proteins has been implicated in multiple lymphomas. The research discovery and clinical application of STATs inhibitors have become an important strategy for treating lymphoma. This review introduces the abnormal activation and mutation of STATs in multiple malignant lymphomas, and focuses on reviewing the latest screening strategies targeting STATs and its clinical application in the treatment of lymphoma, providing references for the further development of STATs inhibitors.

Bioprinted HepG2 cells for studying sonodynamic anticancer activity of chlorine e6 / 药学学报

This paper showed bioprinted HepG2 tumor tissues used for studying the sonodynamic anticancer activity of chlorine e6 (Ce6). HepG2 cells were printed by using alginate/gelatin/hydroxyethyl cellulose composite biomaterial as bio ink and cell viability was detected with Live-Dead assay and MTT proliferation. The ultrasonic intensities of self-built micro ultrasonic device under different powers were estimated by using the temperature change caused by the conversion of acoustic energy to heat energy. Ce6 of 14.3 and 28.6 μg·mL-1 were acted on two-dimensional cultured and three-dimensional printed HepG2 cells, and the antitumor activity of Ce6 was detected by MTT method with ultrasound intensity of 0.15 W·cm2 for 60 s. The results showed that the activities of bioprinted HepG2 cells were as high as 95%, and tumor microspheres were formed after 7 days of culture. The ultrasound intensity was lower than 3 W·cm2, which belonged to low ultrasound intensity and had no damage to normal hepatocyte LO2 cells. By comparing the antitumor activity of Ce6 on 2D cultured and printed HepG2 cells, it was found that the anticancer activity of Ce6 on bioprinted HepG2 cells was 63.4% lower than that on 2D culture cells, indicating the acoustic drug resistance of three-dimensional tumor model. Bioprinted tumor tissues show the potential in the application of in vitro activity evaluation models for sonodynamic therapy.

Detection of progressive and regressive phase and LINE-1 retrotransposon in transfected dogs with transmissible venereal tumor during chemotherapy

Canine transmissible venereal tumor (CTVT) is a tumor that commonly occurs in genital and extragenital sites of both genders. Long interspersed nuclear elements (LINE-1) retrotransposon has a pivotal role in allogenic transfection among uncontrolled dog populations. This study aimed to perform pathomorphological, immunohistochemical, and in situ polymerase chain reaction (PCR) evaluation of CTVT (n = 18) in transfected dogs during chemotherapy. Immunohistochemically, tumor phases were investigated by using specific markers (CD3, CD4, CD8, CD79, and transforming growth factor beta [TGF-β]), and investigated an amplified specific sequence of TVT LINE-1 retrotransposon by in situ PCR. Polyhedral-shaped neoplastic cells that had large, round, hypo/hyperchromatic nuclei and eosinophilic cytoplasm were detected. All marker results were positive, especially in the early weeks of recovery. CD4 and TGF-β markers were conspicuously positive at the initial stage. In situ PCR LINE-1 sequence was initially positive in only four cases. It is believed that the CD and TGF-β markers provide phase identification at tumor initiation and during chemotherapy. It is thought that presence of T and B lymphocytes, which have roles in cellular and humoral immunity, is needed so that regression of the tumor is possible.

Working Mode Exploration for Antineoplastic Clinical Pharmacists Participating in Clinical Rational Drug Use / 中国药师

Objective:To explore the ideas and techniques of antineoplastic clinical pharmacists in clinical practice. Methods:Antineoplastic clinical pharmacists studied the pharmacology, pharmacokinetics and pharmacodynamics of common antineoplastic a-gents,mastered clinical practice guidelines and expert consensus for common tumors and their complications, dealt with and summa-rized the participation in clinical practice. Results:Pharmacists preliminarily set out the antitumor adjuvant directory,and participated in the clinical rational drug use through the following aspects as the breakthrough points: reforming the doctor's advice, reconsidering wisely on health care,evaluating medicine temporary purchase and formulating clinical pathways. Conclusion:Antineoplastic clinical pharmacists can better promote the control of drug proportion and ensure the safety of patients.

Atypical Teratoid Rhabdoid Tumour : From Tumours to Therapies

Atypical teratoid rhabdoid tumours (ATRTs) are the most common malignant central nervous system tumours in children ≤1 year of age and represent approximately 1–2% of all pediatric brain tumours. ATRT is a primarily monogenic disease characterized by the bi-allelic loss of the SMARCB1 gene, which encodes the hSNF5 subunit of the SWI/SNF chromatin remodeling complex. Though conventional dose chemotherapy is not effective in most ATRT patients, high dose chemotherapy with autologous stem cell transplant, radiotherapy and/or intrathecal chemotherapy all show significant potential to improve patient survival. Recent epigenetic and transcriptional studies highlight three subgroups of ATRT, each with distinct clinical and molecular characteristics with corresponding therapeutic sensitivities, including epigenetic targeting, and inhibition of tyrosine kinases or growth/lineage specific pathways.

Endocrine Treatment-Related Symptoms and Patient Outcomes in Breast Cancer: A Meta-Analysis / 한국유방암학회지

PURPOSE: An association between endocrine treatment-related symptoms and breast cancer recurrence has been suggested previously; however, conflicting results have been reported. We performed a meta-analysis of published studies to clarify this relationship. METHODS: We systematically searched PubMed, Embase, Scopus, and the Cochrane database for studies investigating the association between endocrine treatment-related symptoms and patient survival. Random-effects meta-analysis was conducted with recurrence rate as the primary outcome. RESULTS: Out of 7,713 retrieved articles, six studies were included. In patients who received endocrine treatment, the presence of any endocrine treatment-related symptom was found to be associated with a lower recurrence rate in comparison to an absence of any symptoms (hazard ratio [HR], 0.76; 95% confidence interval [CI], 0.66–0.87). This relationship persisted in patients presenting with only vasomotor or only musculoskeletal symptoms (HR, 0.74, 95% CI, 0.63–0.87; HR, 0.69, 95% CI, 0.55–0.86, respectively). At both time-points of symptom evaluation (3 months and 12 months), patients with endocrine treatment-related symptoms had a lower recurrence rate (HR, 0.74, 95% CI, 0.66–0.84; HR, 0.79, 95% CI, 0.69–0.90, respectively). This association was also significant in pooled studies including patients with and without baseline symptoms (HR, 0.73, 95% CI, 0.54–0.99; HR, 0.76, 95% CI, 0.69–0.85, respectively). CONCLUSION: Endocrine treatment-related symptoms are significantly predictive of lower recurrence rate in breast cancer patients, regardless of the type of symptoms, time-point of evaluation, or inclusion of baseline symptoms. These symptoms could be biomarkers for the prediction of long-term responses to endocrine treatment in patients with breast cancer.

Atypical Teratoid Rhabdoid Tumour : From Tumours to Therapies

Atypical teratoid rhabdoid tumours (ATRTs) are the most common malignant central nervous system tumours in children ≤1 year of age and represent approximately 1–2% of all pediatric brain tumours. ATRT is a primarily monogenic disease characterized by the bi-allelic loss of the SMARCB1 gene, which encodes the hSNF5 subunit of the SWI/SNF chromatin remodeling complex. Though conventional dose chemotherapy is not effective in most ATRT patients, high dose chemotherapy with autologous stem cell transplant, radiotherapy and/or intrathecal chemotherapy all show significant potential to improve patient survival. Recent epigenetic and transcriptional studies highlight three subgroups of ATRT, each with distinct clinical and molecular characteristics with corresponding therapeutic sensitivities, including epigenetic targeting, and inhibition of tyrosine kinases or growth/lineage specific pathways.

Synthetic phosphoethanolamine: the state of the art of scientific production

ABSTRACT Cancer is a multifactorial disease and a serious public health problem. Currently, alternative drug treatments for cancer are actively being sought, which is the case of synthetic phosphoethanolamine (PHOS-S), a compound that could possibly have anticarcinogenic effects. To analyze the available scientific evidence to evaluate the anticarcinogenic effects of in vivo and in vitro PHOS-S. A systematic literature review of scientific articles aimed at evaluating the anticarcinogenic potential of PHOS-S, in vivo and in vitro, using the databases PubMed, ScienceDirect, SciElo, CAPES Portal and LILACS. The selected papers suggest a possible anticarcinogenic effect of PHOS-S by inhibiting tumor growth by inducing apoptosis and cell cycle blockade as well as cytotoxic potential against leukemia cells. However, a possible stimulatory effect of tumor growth was also observed. Although some of the evaluated studies indicated a possible anticarcinogenic effect of PHOS-S, the limitations of these studies must be evaluated. Most were performed by the same research group, and in the scientific literature, we identified only preclinical studies (in cells or in animals). No human study has been published. Thus, more studies are needed to confirm the anticarcinogenic capacity of PHOS-S.

Formulation, development and evalution of an immediate release tablet of Methotrexate.

Methotrexate is a Folic Acid Antagonist and used as an Antineoplastic agent. In this study Methotrexate immediate release tablet is developed, which was stable and bioequivalent generic tablet formulation equivalent to innovator’s product. The developed tablet formulation shows similar dissolution and disintegration profile as that of innovator tablet. The immediate release tablet was prepared by Wet Granulation method. The in vitro release was carried out in 0.1N Hydrochloric Acid. The in-vitro release at 50 rpm showed similar dissolution profile when compared with the innovator tablet. The stability studies were carried out and there was no significant change in the drug content, assay, and DT and dissolution rate.

Correlation between chemosensitivity testing and expression of P-gp,LRP in esophageal carcinoma cell cultured in vitro / 国际肿瘤学杂志

Objective To study the correlation between chemotherapy drug sensitivity and the expression of P-glycoprotein protein(P-gp),lung resistant-related protein(LRP)in different esophageal carcinoma patients,which will offer experimental evidence for clinical individualized chemotherapy of esophageal carcinoma patients.Methods Selected fresh esophageal carcinoma's tissue,Common used drugs and chemoscheme for esophageal carcinoma were used for chemosensitivity testing of the primary cultured tumor cells.At the same time,immunohistochemistry method was used to detect the expression of P-gp and LRP of esophageal carcinoma cells.Results The chemotherapy drug sensitivity of single drug was different(P＜0.05).The combination of Tax and DDP had the best effect.DDP and NVB combination had a better effect than DDP and 5-FU combination.The sensitivity of DDP had no significant correlations with expression intensity of P-gp(P＞0.05),and it had significant correlation with expression intensity of LRP(P＜0.05).There were significant correlations between sensitivity of both NVB group and Tax group and expression intensity of P-gp and LRP(P＜0.05).There was no significant correlations between sensitivity of 5-FU and expression intensity of P-gp and LRP(P＞0.05).Conclusion The esophageal carcinoma chemosensitivity in vitro can indicate the sensitive drug of different patients,and guide individualized chemotherapy.The expression of P-gp and LRP has relationship with several chemotherapy drugs,which can provide base for individualized chemotherapy in clinic.

Ocecupational Leukopenia among Nurses:Correlative Factors of Chemotherapeutic Agents / 中华医院感染学杂志

OBJECTIVE To search for the correlative factors among nurses with leukcopenia who occupationally contacted with chemotherapeutic agents,so as to increase their occupational protecting level.METHODS Totally 1232 nurses who occupationally contacted with chemotherapeutic agents from 24 hospitals were investigated by a stratified sampling method.The factors leading to leukopenia were surveyed and analyzed.RESULTS The leukopeuia was prominently correlated with five factors,namely nurses' protective knowledge,protective manipulation scoring,protective condition,exposure index and kinds of agents.CONCLUSIONS Low occupational protecting level can lead to leukopenia.A supporting system based on the occupational health and safety management must be established to insure the clinical nurses' health level.

Microarray comparative genomic hybridization analysis of chromosomal changes in advanced serous ovarian carcinoma / 부인종양

OBJECTIVE: Ovarian cancer is the leading cause of death in women with gynecological malignancies. The purpose of this study was to search characteristic genetic changes in advanced serous ovarian carcinomas using microarray comparative genomic hybridization (mCGH) and to identify genomic alterations specific to chemoresistant disease. METHODS: Genetic changes of 17 primary ovarian tumors were analyzed by MACArrayTM-Karyo 4 K BAC-chip. All the patients had stage IIIc serous ovarian cancer optimally debulked and were initially treated with 6 cycles of platinum-based combination chemotherapy. Ten patients who progressed within 12 months from initial chemotherapy were defined as chemoresistant disease (control group), whereas 7 patients who did not recur for more than 36 months were defined as chemosensitive disease (study group). RESULTS: In control group, the mean number of clones with gain and loss was 288 (7.2%) and 508 (12.7%), respectively. In study group, the mean number of clones with gain and loss was 450 (11.3%) and 860 (21.5%), respectively. In study group, loss of DNA copy number was more frequent than gain (p=0.007). The chromosomal regions with gain of DNA copy numbers in more than 70% of each group were 1p36.33, 3q26.2, 8q24.3, 10q26.3, 12p11.21, 20q13.33, and 21q22.3, while the regions with loss of DNA copy number were 4p12, 5q13.2, 7q11.21, 8p23.1, 14q32.33, Xq13.3-Xq21.1, and Xq21.31. The more frequent chromosomal gains in study group were on 5p15.33 and 14q11.2, while the loss were on 4q34.2, 4q35.2, 5q15, 8p21.1, 8p21.2, 11p15.5, 13q14.13, 13q14.2, 13q32.1, 13q34, 16q22.2, 17p11.2, 17p12, and 22q12.3. CONCLUSION: In this mCGH analysis, common chromosomal abnormalities specific to serous ovarian carcinoma were identified. This study suggests that several genomic aberrations might be related to chemoresistant phenotype in patients with advanced serous ovarian cancer.

In vitro study about the inhibitory effect of CDAⅡ in combination with sodium butyrate on breast cancer cells / 北京大学学报(医学版)

Objective:To investigate if the combined use of CDAⅡ and sodium butyrate can induce demethylation and re-expression of retinoic acid receptor?2(RAR?2)gene in cultured human breast cancer cells MCF7.To explore if the two drugs can inhibit cell growth and induce cell apoptosis synergetically.Methods:MCF7 cell line was treated with CDAⅡ,sodium butyrate,combination of the two drugs respectively.Methylation was assessed by methylation-specific polymerase chain reaction(MSP)for RAR?2 gene.Gene expression was evaluated by reverse transcription polymerase chain reaction(RT-PCR).Apoptosis was detected by terminal deoxynucleotidyl transferase mediated dUTP-biotin nick end labeling(TUNEL)and Hoechst33342/propidiumiodide(PI)staining.Cell growth inhibition was measured by MTT assay.Results:Neither CDAⅡ nor sodium butyrate induced demethylation and re-expression of RAR?2 gene,Combination of the two drugs partially demethylated gene promoter accompanied by re-expression of RAR?2.The apoptotic cells in the double-drug group were obvious following Hoechst33342/PI staining.The percentage of apoptotic cells in the double-drug group was significantly higher than that of the two single-drug group(39.5% vs 5.2%,8.1%)(P