Mutation patterns in recurrent and/or metastatic oropharyngeal squamous cell carcinomas in relation to human papillomavirus status

xloma.fota13 shared this article with you from Inoreader Mutation patterns in recurrent and/or metastatic oropharyngeal squamous cell carcinomas in relation to human papillomavirus status Via Cancer Medicine A subgroup of 13–25% of HPV‐driven (HPV+) OPSCC patients develop local or distant recurrence (LDR) and a severe course of disease similar to that of patients with HPV‐negative (HPV‐) OPSCC. Regarding the genes analyzed, we found that the HPV+OPSCC of patients with LDR carried a higher number of mutations than HPV+OPSCC of patients without LDR, with a similar mutation frequency as the HPV−OPSCC of LDR patients. Surprisingly, HPV−OPSCC of patients who did not develop LDR showed the highest number of mutations, suggesting that not the number but specific driver mutations are dominant factors for recurrence and that tumor‐specific neoantigens may play a role in a supportive antitumor immune response after therapy. Abstract Patients with HPV‐driven (HPV+) oropharyngeal squamous cell carcinoma (OPSCC) have a significantly improved overall survival compared to patients with HPV‐negative (HPV−) OPSCC. Nevertheless, 13%–25% of patients with HPV+OPSCC develop local/distant recurrence (LDR) and have a course of disease similar to HPV−OPSCC. We hypothesize that HPV+OPSCCs of patients with LDR have a mutation frequency and pattern similar to HPV−OPSCCs, which is associated with severe outcome. We performed targeted next‐generation sequencing using a customized gene panel and compared data from 56 matched HPV+and HPV−OPSCC of patients with/without LDR regarding protein‐altering variants. Despite improved overall survival of patients with HPV+OPSCC, those who develop LDR show a strongly reduced survival rate that is similar or even worse compared to HPV−OPSCC patients. Overall, the number of mutations was similar in OPSCC of patients with and without LDR. In total and with respect to TP5 3, HPV−OPSCC had significantly more protein‐altering mutations than HPV+OPSCC. The number of mutations was similar in HPV−OPSCC of patients with and without LDR with the exception of FAT1, which was mutated more frequently in patients without LDR. In HPV+OPSCC, HRAS, PIK3R1, STK11 and TP63 were more frequently mutated in patients with LDR compared to patients without. HPV+OPSCC of patients with LDR have a similar mutation pattern as HPV−OPSCC, except TP53, which was mutated to a significantly lower extent. In conclusion, HPV−and HPV+OPSCC with LDR have similar mutation counts in the analyzed genes. We suspect that the number of mutations is not causal for disease progression, rather specific mutations could be important. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Comparison of efficacy, safety, patients’ quality of life, and doctors’ occupational stress between lenalidomide‐based and bortezomib‐based induction in patients with newly diagnosed multiple myeloma

xloma.fota13 shared this article with you from Inoreader Comparison of efficacy, safety, patients' quality of life, and doctors' occupational stress between lenalidomide‐based and bortezomib‐based induction in patients with newly diagnosed multiple myeloma Via Cancer Medicine Compared to PAD, RAD induction had a comparable efficacy and significantly better safety profile, improved quality of life for patients and reduced occupational stress for doctors. However, RAD had an effect on stem cell collection, which may need to be limited to 4 cycles to avoid irreversible damage to hematopoietic stem cells. Abstract Background In the new therapeutic era, comparisons between regimens containing lenalidomide and bortezomib are needed. Methods In this single‐center, prospective study, patients received four to six cycles of lenalidomide+liposomal doxorubicin+dexamethasone (RAD) or bortezomib+liposomal doxorubicin+dexamethasone (PAD) every 4 weeks, with subsequent autologous stem cell transplantation (ASCT) and maintenance therapy. We compared the efficacy, safety, patients' quality of life, and doctors' occupational stress between RAD and PAD induction in newly diagnosed MM patients. Results The complete response (CR) rate was comparable between the RAD and PAD groups after induction (30.8% vs. 32.0%, p = 0.92). Common adverse events, including infections, peripheral neuropathy, and gastrointestinal disturbances, were more frequent in the PAD group, while leukopenia and rashes were more common in the RAD group. Compared with PAD, RAD improved patients' quality of life more quickly and caused less occupational stress for doctors. However, only 31.6% of patients collected adequate CD34+ cells (≥2 × 106/kg) in the RAD group, which was significantly lower than that in the PAD group (95.5%, p < 0.001). The number of CD34+ cells collected was significantly higher in patients within three courses of RAD than in patients with four or five to six courses (14.18 ± 13.57 vs. 2.07 ± 2.42 vs. 1.51 ± 1.81 × 106/kg, p = 0.028). The median progression ‐free survival and overall survival of the two groups were not reached by the end of follow‐up. Conclusion Compared to PAD, RAD induction had comparable efficacy and a significantly better safety profile, improved quality of life for patients, and reduced occupational stress for doctors. However, RAD induction may need to be limited to four cycles to avoid irreversible damage to hematopoietic stem cells. Clinical trial registration This study was registered at www.chictr.org.cn (ChiCTR1900021558). View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Cancer survivorship in hematologic malignancies: Lifestyle changes after diagnosis

xloma.fota13 shared this article with you from Inoreader Cancer survivorship in hematologic malignancies: Lifestyle changes after diagnosis Via Cancer Medicine Patients exhibit significant lifestyle changes after being diagnosed with a hematologic malignancy. Clinicians should take advantage of this "teachable moment" at the time of diagnosis to educate patients about positive health behavior changes. Abstract Background Studies show that patients make lifestyle changes soon after certain solid tumor diagnoses, suggesting that this may be a teachable moment to motivate and promote healthy behaviors. There is a paucity of data regarding changes made after a diagnosis of a hematologic malignancy. Methods A cross‐sectional study of 116 patients at a community oncology center who completed anonymous questionnaires was performed. Questions addressed lifestyle choices made with respect to smoking, alcohol consumption, recreational drug use, diet, and exercise habits before and after diagnosis of a hematologic malignancy. Support systems utilized, including psychiatry services, were also assessed. Results Patients exhibited significant reduction in smoking behavior (Χ 2 = 31.0, p < 0.001). 82.4% (n = 14) of one pack per day smokers quit between the time periods, with nearly all smokers showing a reduction after diagnosis. Alcohol use overall did not change significantly, however, 10.3% (n = 12) of patients reported quitting drinking completely between time periods. Changes in dietary intake and exercise were not statistically significant overall. Utilization of external support systems correlated with improved diet as well as decrease in total smoking years. Conclusions This study demonstrates that patients exhibited significant lifestyle changes after being diagnosed with a hematologic malignancy. Clinicians should take advantage of this 'teachable moment' to educate patients about positive health behavior changes. Advances in cancer therapeutics have led to an increase in cancer survivors, this education is crucial in reducing the risk of developing chronic comorbidities as well as secondary malignancies. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

The optimal cut‐off value in fit‐based colorectal cancer screening: An observational study

xloma.fota13 shared this article with you from Inoreader The optimal cut‐off value in fit‐based colorectal cancer screening: An observational study Via Cancer Medicine If 24 colonoscopies needed to detect one cancer is acceptable for the health care system and the participants, the optimal cut‐off value in fecal immunochemical test screening is 45 ng Hb/ml. When only 19/16/14/10 colonoscopies are accepted to find one cancer, then, the optimal cut‐off value is 80/125/175/350 ng Hb/ml. Abstract Background Colorectal cancer (CRC) screening programs using fecal immunochemical test (FIT) have to choose a cut‐off value to decide which citizens to recall for colonoscopy. The evidence on the optimal cut‐off value is sparse and based on studies with a low number of cancer cases. Methods This observational study used data from the Danish Colorectal Cancer Screening Database. Sensitivity and specificity were estimated for various cut‐off values based on a large number of cancers. Traditionally optimal cut‐off values are found by weighting sensitivity and specificity equally. As this might result in too many unnecessary colonoscopies we also provide optimal cut‐off values for different weighting of sensitivity and specificity/number of needed colonoscopies to detect one cancer. Results Weighting sensitivity and specificity equally gives an optimal cut‐off value of 45 ng Hb/ml. This, however, means making 24 colonoscopies to detect one cancer. Weighting sensitivity lower and for example, aiming at making about 16 colonoscopies to detect one cancer, gives an optimal cut‐off value of 125 ng Hb/ml. Conclusions The optimal cut‐off value in an FIT population‐based screening program is 45 ng Hb/ml, when as traditionally sensitivity and specificity are weighted equally. If, however, 24 colonoscopies needed to detect one cancer is too huge a burden on the health care system and the participants, 80, 125, 175, and 350 ng Hb/ml are optimal cut‐off values when only 19/16/14/10 colonoscopies are accepted to find one cancer. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Plasma metabolomic profile associated with fatigue in cancer patients

xloma.fota13 shared this article with you from Inoreader Plasma metabolomic profile associated with fatigue in cancer patients Via Cancer Medicine We found significant metabolomic profile differences associated with cancer‐related fatigue. Potentially impactful metabolic pathways associated specifically with fatigued cancer patients include changes in metabolites associated with sphingolipid metabolism, histidine metabolism, and cysteine and methionine metabolism. Abstract Background Metabolomics is the newest ‐omics methodology and allows for a functional snapshot of the biochemical activity and cellular state. The goal of this study is to characterize metabolomic profiles associated with cancer‐related fatigue, a debilitating symptom commonly reported by oncology patients. Methods Untargeted ultrahigh performance liquid chromatography/mass spectrometry metabolomics approach was used to identify metabolites in plasma samples collected from a total of 197 participants with or without cancer. Partial least squares‐discriminant analysis (PLS‐DA) was used to identify discriminant metabolite features, and diagnostic performance of selected classifiers was quantified using area under the receiver operating characteristics (AUROC) curve analysis. Pathway enrichment analysis was performed using Fisher's exact test and the Kyoto Encyclopedia of Genes and Genomes (KEGG) metabolic pathway database. Findings The global metabolomics approach yielded a total of 1120 compounds of known identity. Significant metabolic pathways unique to fatigued cancer versus control groups included sphingolipid metabolism, histidine metabolism, and cysteine and methionine metabolism. Significant pathways unique to non‐fatigued cancer versus control groups included inositol phosphate metabolism, primary bile acid biosynthesis, ascorbate and aldarate metabolism, starch and sucrose metabolism, and pentose and glucuronate interconversions. Pathways shared between the two comparisons included caffeine metabolism, tyrosine metabolism, steroid hormone biosynthesis, sulfur metabolism, and phenylalanine metabolism. Conclusions We found significant metabolomic profile differences associated with cancer‐related fatigue. By comparing metabolic signatures unique to fatigued cancer patients with metabolites associated with, but not unique to, fatigued cancer individuals (overlap pathways) and metabolites associated with cancer but not fatigue, we provided a broad view of the metabolic phenotype of cancer‐related fatigue. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Electrostatics Favor PNA : DNA Stability over Stereochemistry in Pyrrolidine‐Based Cationic Dual‐Backbone PNA Analogues

xloma.fota13 shared this article with you from Inoreader Electrostatics Favor PNA : DNA Stability over Stereochemistry in Pyrrolidine‐Based Cationic Dual‐Backbone PNA Analogues Via European Journal of Organic Chemistry A dual diaminopyrrolidine based peptide nucleic acid (dapPNA) monomer that give rise to two different PNA backbones (shown in blue & red) was synthesized using orthogonal solid phase chemistry. Presence of free amino group makes PNA cationic and thus not only show high thermal stability in complexation with DNA but also overcomes the unfavorable stereochemical effects. Abstract Modifications to the peptide nucleic acid (PNA) backbone has been well known to alter the thermodynamical parameters of PNA : DNA complexes to broaden their utility for different applications. Electrostatic interactions between a modified PNA having a positively charged backbone and the negatively charged DNA has been shown to enhance thermal stabilities of PNA : DNA complexes at various instances. On the other hand, chiral introduction in PNA backbone leads to stereochemical preference that affects binding properties. However, the interplay between electrostatics and stereochemistry has not been systematically studied so far. Herein, we report the synthesis and biophysical characterization of cationic PNA named dapPNA, first of its kind, having a dual PNA backbone constituting of a pyrrolidine ring having a β‐substitution. One of the aims of this study was to investigate the role of electrostatics over stereochemical preferences. The results show that electrosta tic attraction between cationic dapPNA and negatively charged DNA overcomes the unfavorable stereochemical effects and enhances stability of PNA : DNA complexes. Moreover, two different PNA backbones derived from a single PNA monomer expands the repertoire of pyrrolidine based PNA analogues. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Triptycene Boronates, Boranes, and Boron Ate‐Complexes: Toward Sterically Hindered Triarylboranes and Trifluoroborates

xloma.fota13 shared this article with you from Inoreader Triptycene Boronates, Boranes, and Boron Ate‐Complexes: Toward Sterically Hindered Triarylboranes and Trifluoroborates Via European Journal of Organic Chemistry Two synthetic strategies towards bulky boranes, boronates and boron ate‐complexes derived from triptycenes have been developed. These approaches started from borylated or brominated anthracenes and involved a Br/Li exchange and [4+2] cycloaddition reaction with in‐situ generated benzyne to produce a series of triptycene boronates and borates substituted in positions 1 or 9 with various boron substituents such as BPin, Bneo, BF 3 K and B(Mes) 2 . X‐ray diffraction crystallographic analysis and UV‐Vis/fluorimetric measurements provided quantitative information on the effect of the triptycene scaffold on their structure and their photophysical and electronic properties. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Reverse hybrid therapy for Helicobacter pylori eradication

xloma.fota13 shared this article with you from Inoreader Message: The standard hybrid regimen is functionally a combination of sequential therapy and concomitant therapy as it consists of a proton pump inhibitor (PPI) and amoxicillin for 10-14 d with the addition of clarithromycin and metronidazole for the final 7 d (i.e., a 2 + 4 regimen). Reverse hybrid therapy is a combination of sequential and concomitant therapy, using the same drugs as hybrid therapy, but in reverse sequence, as follows: PPI plus amoxicillin plus 2 other antibiotics (usually, clarithromycin and metronidazole) for 7 days then. PPI plus amoxicillin for 3–7 days. Reverse hybrid therapy for Helicobacter pylori eradication: A systematic review and meta‐analysis Via Helicobacter ABSTRACT Background The efficacy and safety of reverse hybrid therapy in the treatment of Helicobacter pylori (H. pylori) infection remained unclear. Materials and Methods This systematic review was performed in accordance with the PRISMA 2009 guidelines. A systematic search of the Pubmed, Embase, and Cochrane database was conducted using the combination of "Helicobacter pylori or H. pylori or Hp" and "hybrid". The primary endpoint of this meta‐analysis was to evaluate the efficacy of reverse hybrid therapy; the second endpoint was to evaluate the efficacy of reverse hybrid therapy among the strains with antibiotic resistance and the compliance, safety of reverse hybrid therapy. Results Four studies with 1530 participants were included. The crude H. pylori eradication rate of reverse hybrid therapy was 95.5% (737/772) and 96.2% (701/729) by ITT and PP analysis, respectively. There is no statistical significance of efficacy between reverse hybrid therapy and control according to ITT (pooled rate: 96% vs. 94%, RR = 1.02, 95% CI, 0.95–1.05, p = .28) and PP (pooled rate: 96% vs. 94%, RR = 1.02, 95% CI, 0.99–1.06, p = .23) analysis. The effect of reverse hybrid therapy in strains with isolated clarithromycin resistance (pooled rate: 89% vs. 65%, RR = 1.13, 95% CI, 0.77–1.66, p = .53), metronidazole resistance (pooled rate: 91% vs. 81%, RR = 1.00, 95% CI, 0.96–1.05, p = .85), and dual clarithromycin‐metronidazole resistance (pooled rate: 86% vs. 83%, RR = 0.94, 95% CI, 0.69–1.27, p = .69) showed no superio r to that of control. The compliance of reverse hybrid therapy is 96%, and side effect is slightly lower to that of control group. Conclusion Reverse hybrid therapy shows good efficacy, safety, and compliance in the treatment of H. pylori infection. However, its application for H. pylori treatment in regions with high antibiotic resistance need to be further explored. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Reverse hybrid therapy for Helicobacter pylori eradication: A systematic review and meta‐analysis

xloma.fota13 shared this article with you from Inoreader Reverse hybrid therapy for Helicobacter pylori eradication: A systematic review and meta‐analysis Via Helicobacter ABSTRACT Background The efficacy and safety of reverse hybrid therapy in the treatment of Helicobacter pylori (H. pylori) infection remained unclear. Materials and Methods This systematic review was performed in accordance with the PRISMA 2009 guidelines. A systematic search of the Pubmed, Embase, and Cochrane database was conducted using the combination of "Helicobacter pylori or H. pylori or Hp" and "hybrid". The primary endpoint of this meta‐analysis was to evaluate the efficacy of reverse hybrid therapy; the second endpoint was to evaluate the efficacy of reverse hybrid therapy among the strains with antibiotic resistance and the compliance, safety of reverse hybrid therapy. Results Four studies with 1530 participants were included. The crude H. pylori eradication rate of reverse hybrid therapy was 95.5% (737/772) and 96.2% (701/729) by ITT and PP analysis, respectively. There is no statistical significance of efficacy between reverse hybrid therapy and control according to ITT (pooled rate: 96% vs. 94%, RR = 1.02, 95% CI, 0.95–1.05, p = .28) and PP (pooled rate: 96% vs. 94%, RR = 1.02, 95% CI, 0.99–1.06, p = .23) analysis. The effect of reverse hybrid therapy in strains with isolated clarithromycin resistance (pooled rate: 89% vs. 65%, RR = 1.13, 95% CI, 0.77–1.66, p = .53), metronidazole resistance (pooled rate: 91% vs. 81%, RR = 1.00, 95% CI, 0.96–1.05, p = .85), and dual clarithromycin‐metronidazole resistance (pooled rate: 86% vs. 83%, RR = 0.94, 95% CI, 0.69–1.27, p = .69) showed no superio r to that of control. The compliance of reverse hybrid therapy is 96%, and side effect is slightly lower to that of control group. Conclusion Reverse hybrid therapy shows good efficacy, safety, and compliance in the treatment of H. pylori infection. However, its application for H. pylori treatment in regions with high antibiotic resistance need to be further explored. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Mitogen‐activated protein kinase inhibition‐induced modulation of epidermal growth factor receptor signaling in human head and neck squamous cell carcinoma

xloma.fota13 shared this article with you from Inoreader Mitogen‐activated protein kinase inhibition‐induced modulation of epidermal growth factor receptor signaling in human head and neck squamous cell carcinoma Via Head & Neck Abstract Background Epidermal growth factor receptor (EGFR) overexpression is one of the most notable characteristics in head and neck squamous cell carcinoma (HNSCC). The MAPK kinase (MEK) inhibitor trametinib has shown efficacy to treat HNSCC; however, the molecular mechanism remains unclear. Methods HNSCC lines, mouse models, Western blot, and flow cytometry were employed to analyze the anticancer effects of trametinib. Results The JHU‐011, JHU‐022, and JHU‐029 HNSCC cells with different genetic alterations were highly susceptible to trametinib. Trametinib effectively reduced EGFR expression, which was accompanied by the reduction of pro‐survival protein MYC, and the increased expression of a MYC‐targeted cyclin‐dependent kinase inhibitor p27kip1 and pro‐apoptotic protein BIM. Trametinib resulted in G1 arrest of the cells, markedly reduced cell numbers in S phase, and significantly increased apoptosis. In mouse models, trametinib strongly inhibited tumors growth. Conclusions The MAPK–ERK signaling inhibition by trametinib may target EGFR and the downstream proteins against HNSCC. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Unusual location of a second branchial cleft cyst presenting in the suprasternal notch

xloma.fota13 shared this article with you from Inoreader Unusual location of a second branchial cleft cyst presenting in the suprasternal notch Via Head & Neck Abstract Background Second branchial cleft cysts (SBCCs) are congenital benign tumors that comprise up to 90% of all branchial cleft anomalies. SBCCs typically present in the lateral neck along the anterior border of the upper third of the sternocleidomastoid muscle. We describe a case of a SBCC presenting in an unusual location in the lower neck close to midline. Methods An 18‐year‐old male presented with a 2‐year history of a neck mass in the suprasternal notch. Imaging findings were reviewed with a head and neck radiologist who felt that the findings were highly suggestive of a fourth branchial cleft cyst. Results The patient underwent surgical excision of the mass. Final pathologic evaluation confirmed the diagnosis of a second branchial cleft cyst. Conclusions Though extremely uncommon, second branchial cleft cysts can extend to the suprasternal notch and should not be excluded from the differential diagnoses of lower neck masses. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.