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BACKGROUND AND PURPOSE: Gastrointestinal tumours overexpress voltage-gated calcium (CaV3) channels (CaV3.1, 3.2 and 3.3). CaV3 channels regulate cell growth and apoptosis colorectal cancer. Gossypol, a polyphenolic aldehyde found in the cotton plant, has anti-tumour properties and inhibits CaV3 currents. A systematic study was performed on gossypol blocking mechanism on CaV3 channels and its potential anticancer effects in colon cancer cells, which express CaV3 isoforms. EXPERIMENTAL APPROACH: Transcripts for CaV3 proteins were analysed in gastrointestinal cancers using public repositories and in human colorectal cancer cell lines HCT116, SW480 and SW620. The gossypol blocking mechanism on CaV3 channels was investigated by combining heterologous expression systems and patch-clamp experiments. The anti-tumoural properties of gossypol were estimated by cell proliferation, viability and cell cycle assays. Ca2+ dynamics were evaluated with cytosolic and endoplasmic reticulum (ER) Ca2+ indicators. KEY RESULTS: High levels of CaV3 transcripts correlate with poor prognosis in gastrointestinal cancers. Gossypol blockade of CaV3 isoforms is concentration- and use-dependent interacting with the closed, activated and inactivated conformations of CaV3 channels. Gossypol and CaV3 channels down-regulation inhibit colorectal cancer cell proliferation by arresting cell cycles at the G0/G1 and G2/M phases, respectively. CaV3 channels underlie the vectorial Ca2+ uptake by endoplasmic reticulum in colorectal cancer cells. CONCLUSION AND IMPLICATIONS: Gossypol differentially blocked CaV3 channel and its anticancer activity was correlated with high levels of CaV3.1 and CaV3.2 in colorectal cancer cells. The CaV3 regulates cell proliferation and Ca2+ dynamics in colorectal cancer cells. Understanding this blocking mechanism maybe improve cancer therapies.
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Bloqueadores dos Canais de Cálcio , Canais de Cálcio Tipo T , Proliferação de Células , Neoplasias do Colo , Gossipol , Humanos , Gossipol/farmacologia , Gossipol/análogos & derivados , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/patologia , Neoplasias do Colo/metabolismo , Bloqueadores dos Canais de Cálcio/farmacologia , Proliferação de Células/efeitos dos fármacos , Canais de Cálcio Tipo T/metabolismo , Canais de Cálcio Tipo T/genética , Pontos de Checagem da Fase G1 do Ciclo Celular/efeitos dos fármacos , Cálcio/metabolismo , Linhagem Celular Tumoral , Fase de Repouso do Ciclo Celular/efeitos dos fármacos , Antineoplásicos/farmacologiaRESUMO
Background: Persons living with HIV (PLWH) have a higher risk of persistent infection with human papillomavirus (HPV) and anal cancer. We evaluated knowledge and awareness of HPV infection and risk factors for anal cancer among PLWH in Puerto Rico (PR). Methods: Data from a cross-sectional study (2020-2021) were analyzed (n=212). Inclusion criteria included PLWH, aged ≥ 26 years, and living in PR. Telephone interviews collected information on sociodemographic, lifestyle and clinical characteristics. Two 13-item scales were used to assess knowledge of HPV and anal cancer risk factors; adequate knowledge for both scales were defined as scoring >70%. Logistic regression models using generalized linear models were used to determine the association between 1) HPV infection awareness, 2) HPV infection knowledge, and 3) Anal cancer risk factors knowledge. Results: The median age was 54 years (IQR: 46,58), 67.5% were male, 71.7% reported having an income <$20,000, and 54.3% had an education level of more than high school. HPV awareness was high (82.1%), but only 40.2% and 3.8% had adequate knowledge of HPV and anal cancer risk factors, respectively. In adjusted logistic regression models, men who have sex with men (OR: 1.26, 95%CI: 1.07-1.47) and women (OR: 1.35, 95%CI: 1.15-1.59) aged ≥50 years had higher odds of HPV awareness than heterosexual men in that age group. Moreover, those with history of anal Pap test aged <50 years had more HPV awareness (OR 1.34, 95%CI: 1.08-1.66) than their counterparts. Adequate HPV knowledge was higher among participants with an education level of more than high-school (OR:1.28, 95%CI: 1.10-1.50) and with a history of HPV diagnosis (OR:1.33, 95%CI: 1.08-1.65) than their counterparts. In addition, people with good/very good/excellent health perception had higher odds of HPV knowledge (OR:1.23, 95%CI: 1.03-1.47) than those who reported poor/regular health perception. For anal cancer risk factors, PLWH for ≥15 years had increased odds of having adequate knowledge (OR:1.07, 95%CI: 1.02-1.14) than their counterparts. Conclusions: Despite high awareness of HPV, limited knowledge about HPV and anal cancer risk factors was observed among PLWH. Results from our study highlight the need for educational efforts within this population as an anal cancer prevention strategy.
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Neoplasm of the penis is relatively rare in most regions representing 0-2% of cancers worldwide. While the penis can be affected by sarcomas, basal cell carcinomas or even melanoma, Penile Squamous Cell Carcinoma (PSCC) represents approximately 95% of all penile neoplasms. Despite its rarity and most common presentation at later decades of life most individuals diagnosed with PSCC are faced with significant decrease in quality of life. The prevalence and incidence vary among different regions and populations, but a common trend is for diagnosis to occur late (stage 4). Underdeveloped countries are traditionally reported to have higher incidence rates; however, rates may vary significantly between urban and rural areas even in developed countries. Age adjusted rates are on the rise in some countries that used to have incidence rates of 1:100 000 or less. The list of associated risk factors is long and includes among others, lack of neonatal circumcision, poor genital hygiene, socioeconomic status, history of human papillomavirus (HPV) infection and penile intraepithelial neoplasia (PeIN). Many risk factors are widely debated among experts however HPV and PeIN are indisputable risk factors, and both also form part of the classification system for PSCC. Both conditions may have occurred in the past or be present at the time of diagnosis and identifying them plays a major role in management strategies. For such a rare condition PSCC can present in many different forms clinically making diagnosis no easy feat. Diagnosis of PSCC is done through clinical examination, including lymph node palpation, followed by a biopsy, which is essential for the classification. Lymph node involvement is a common finding at first presentation and investigation of spread to deep nodes is important and can be done with the aid of PET-CT. Treatment options for PSCC include surgery, chemotherapy, and radiation therapy. Surgical removal of the tumor is considered the most effective however can lead to severe decrease of quality of life. Chemotherapy is used in the case of fixed or bulky lymph nodes, where surgery is not indicated, and for distant metastasis. Radiation therapy is particularly effective in the case of HPV-positive PSCC.
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French Guiana is a French territory in South America. The exposome of persons living there is quite different from that in mainland France and the ethnic make-up of the population is also quite different. Poverty is also widespread with difficulties in accessing care magnified by the low medical-professional density. In this singular context, we aimed to measure the incidence of pediatric cancers and to compare it with other continents. We used French Guiana's certified cancer registry to study this between 2003 and 2017. Incidences were standardized using the world population with three strata: 0-4 years, 5-9 years, and 10-14 years. There were 164 solid tumors or hematologic malignancies diagnosed in children under the age of 15 (92 in boys and 72 in girls). Over the study period, the standardized incidence rate was 14.1 per 100,000 among children aged under 15 years. There was no significant trend during the study period. The three most common causes of cancer were leukemias-mostly lymphoblastic-CNS tumors, and sarcoma. The standardized incidence of pediatric cancers in French Guiana was similar to those in Western Europe and North America. As others have discovered, we found that males tended to be more likely to develop cancer, notably leukemia, CNS tumors, sarcoma, and retinoblastoma. As elsewhere, the predominant cancer types changed with age. Our initial assumption was that given the singular context of French Guiana, there may have been differences in pediatric cancer incidences. Here we showed that overall, contrary to our assumption and to trends in tropical countries, the incidence of pediatric cancers was in a range between Western Europe and North America with some apparent but non-significant differences in the main types of cancers observed in global statistics. Quality cancer registry data in this tropical region confirm the suspicion that lower incidences in tropical low- and middle-income countries are likely to result from incomplete diagnosis and data collection.
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Acute leukemias present therapeutic challenges despite advances in treatments. Microtubule inhibitors have played a pivotal role in cancer therapy, inspiring exploration into novel compounds like C2E1 from the cyclopenta[b]indole class. In the present study, we investigated C2E1's potential as a therapeutic agent for acute leukemia at molecular, cellular, and genetic levels. C2E1 demonstrated tubulin depolarization activity, significantly reducing leukemia cell viability. Its impact involved multifaceted mechanisms: inducing apoptosis, arrest of cell cycle progression, and inhibition of clonogenicity and migration in leukemia cells. At a molecular level, C2E1 triggered DNA damage, antiproliferative, and apoptosis markers and altered gene expression related to cytoskeletal regulation, disrupting essential cellular processes crucial for leukemia cell survival and proliferation. These findings highlight C2E1's promise as a potential candidate for novel anti-cancer therapies. Notably, its distinct mode of action from conventional microtubule-targeting drugs suggests the potential to bypass common resistance mechanisms encountered with existing treatments. In summary, C2E1 emerges as a compelling compound with diverse effects on leukemia cells, showcasing promising antineoplastic properties. Its ability to disrupt critical cellular functions selective to leukemia cells positions it as a candidate for future therapeutic development.
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Antineoplásicos , Apoptose , Sobrevivência Celular , Indóis , Leucemia , Moduladores de Tubulina , Humanos , Leucemia/tratamento farmacológico , Moduladores de Tubulina/farmacologia , Indóis/farmacologia , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Tubulina (Proteína)/metabolismo , Dano ao DNA/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Microtúbulos/efeitos dos fármacosRESUMO
Endometriosis is an estrogen-dependent inflammatory disease, defined by the presence of functional endometrial tissue outside of the uterine cavity. This disease is one of the main gynecological diseases, affecting around 10%-15% women and girls of reproductive age, being a common gynecologic disorder. Although endometriosis is a benign disease, it shares several characteristics with invasive cancer. Studies support that it has been linked with an increased chance of developing endometrial ovarian cancer, representing an earlier stage of neoplastic processes. This is particularly true for women with clear cell carcinoma, low-grade serous carcinoma and endometrioid. However, the carcinogenic pathways between both pathologies remain poorly understood. Current studies suggest a connection between endometriosis and endometriosis-associated ovarian cancers (EAOCs) via pathways associated with oxidative stress, inflammation, and hyperestrogenism. This article aims to review current data on the molecular events linked to the development of EAOCs from endometriosis, specifically focusing on the complex relationship between the immune response to endometriosis and cancer, including the molecular mechanisms and their ramifications. Examining recent developments in immunotherapy and their potential to boost the effectiveness of future treatments.
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Human papillomavirus (HPV) infection is one of the most common sexually transmitted infections worldwide. It is caused by the HPV, a DNA virus that infects epithelial cells in various mucous membranes and skin surfaces. HPV can be categorised into high-risk and low-risk types based on their association with the development of certain cancers. High-risk HPV types, such as HPV-16 and HPV-18, are known to be oncogenic and are strongly associated with the development of cervical, anal, vaginal, vulvar, penile, and oropharyngeal cancers. These types of HPV can persist in the body for an extended period and, in some cases, lead to the formation of precancerous lesions that may progress to cancer if left untreated. Low-risk HPV types, such as HPV-6 and HPV-11, are not typically associated with cancer but can cause benign conditions like genital warts. Genital warts are characterised by the growth of small, cauliflower-like bumps on the genital and anal areas. Although not life-threatening, they can cause discomfort and psychological distress. HPV is primarily transmitted through sexual contact, including vaginal, anal, and oral sex. It can also be transmitted through non-penetrative sexual activities that involve skin-to-skin contact. In addition to sexual transmission, vertical transmission from mother to child during childbirth is possible but relatively rare. Prevention of HPV infection includes vaccination and safe sexual practices. HPV vaccines, such as Gardasil and Cervarix, are highly effective in preventing infection with the most common high-risk HPV types. These vaccines are typically administered to adolescents and young adults before they become sexually active. Safe sexual practices, such as consistent and correct condom use and limiting the number of sexual partners, can also reduce the risk of HPV transmission. Diagnosis of HPV infection can be challenging because the infection is often asymptomatic, especially in men. In women, HPV testing can be done through cervical screening programs, which involve the collection of cervical cells for analysis. Abnormal results may lead to further diagnostic procedures, such as colposcopy or biopsy, to detect precancerous or cancerous changes. Overall, HPV infection is a prevalent sexually transmitted infection with significant implications for public health. Vaccination, regular screening, and early treatment of precancerous lesions are key strategies to reduce the burden of HPV-related diseases and their associated complications. Education and awareness about HPV and its prevention are crucial in promoting optimal sexual health. This study aimed to carry out a literature review considering several aspects involving HPV infection: Global distribution, prevalence, biology, host interactions, cancer development, prevention, therapeutics, coinfection with other viruses, coinfection with bacteria, association with head and neck squamous cell carcinomas, and association with anal cancer.
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Neoplasias , Infecções por Papillomavirus , Humanos , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/virologia , Infecções por Papillomavirus/prevenção & controle , Infecções por Papillomavirus/transmissão , Neoplasias/virologia , Neoplasias/epidemiologia , Neoplasias/prevenção & controle , Papillomaviridae/fisiologia , Papillomaviridae/genética , Papillomaviridae/patogenicidade , Vacinas contra Papillomavirus/administração & dosagem , Vacinas contra Papillomavirus/imunologia , Interações entre Hospedeiro e Microrganismos , Feminino , MasculinoRESUMO
BACKGROUND: Anlotinib has demonstrated promising anti-tumor efficacy in various solid tumors. Additionally, there is evidence suggesting that immune therapy can enhance the systemic responses of anlotinib. This study aimed to assess the effectiveness and safety of combining anlotinib with PD-1 inhibitors compared to fluoropyrimidine-based chemotherapy as a second-line treatment option for advanced biliary tract cancers (BTCs). METHODS: A total of 242 patients with BTCs were screened at the First Affiliated Hospital of Zhengzhou University from October 2015 to October 2022. Among them, 78 patients who received either anlotinib plus PD-1 inhibitors (AP) or fluoropyrimidine-based chemotherapy (FB) as second-line treatment were included in the study. The primary endpoint was progression-free survival (PFS), and the secondary endpoints included objective response rate (ORR), disease control rate (DCR), overall survival (OS), safety, and predictive tumor biomarkers. RESULTS: Among the 78 patients with BTCs, 39 patients received AP, while 39 patients were administered FB. The ORR in the AP group was 20.5%, compared to 5.1% in the FB group. The DCR was 87.2% in the AP group and 66.7% in the FB group. The AP group demonstrated significantly better ORR and DCR compared to the FB group (p = 0.042, p = 0.032). The median PFS and OS in the AP group were 7.9 months (95% CI: 4.35-11.45) and 13.9 months (95% CI: 5.39-22.41), respectively. In the FB group, the median PFS and OS were 4.1 months (95% CI: 3.17-5.03) and 13.2 months (95% CI: 8.72-17.68), respectively. The AP group exhibited significantly better median PFS than the FB group (p = 0.027). In the subgroup analysis, patients without liver metastasis had a much longer PFS in the AP group compared to the FB group (14.3 vs. 5.5 months, p = 0.016). Similarly, patients with CEA ≤ 5 µg/L also demonstrated a longer PFS in the AP group compared to the FB group (8.7 vs. 3.9 months, p = 0.008). CONCLUSIONS: The combination of anlotinib and PD-1 inhibitors demonstrated a promising clinical effect compared to fluoropyrimidine-based chemotherapy in the second-line treatment of refractory advanced BTCs. Liver metastases and CEA levels may serve as predictive factors for identifying patients who may benefit from AP therapy.
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Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias do Sistema Biliar , Inibidores de Checkpoint Imunológico , Indóis , Quinolinas , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Quinolinas/uso terapêutico , Quinolinas/efeitos adversos , Quinolinas/administração & dosagem , Neoplasias do Sistema Biliar/tratamento farmacológico , Neoplasias do Sistema Biliar/patologia , Neoplasias do Sistema Biliar/mortalidade , Idoso , Indóis/uso terapêutico , Indóis/administração & dosagem , Indóis/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Adulto , Inibidores de Checkpoint Imunológico/uso terapêutico , Inibidores de Checkpoint Imunológico/efeitos adversos , Inibidores de Checkpoint Imunológico/administração & dosagem , Intervalo Livre de Progressão , Estudos Retrospectivos , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Idoso de 80 Anos ou maisRESUMO
Precision medicine has helped identify several tumor molecular aberrations to be treated with targeted therapies. These therapies showed substantial improvement in efficacy without excessive toxicity in patients with specific oncogenic drivers with advanced cancers. In metastatic lung cancers, the implementation of broad platforms for molecular tumor sequencing has helped oncology providers identify oncogenic drivers linked with better outcomes when treated upfront with targeted therapies. Mesenchymal-epithelial transition factor (MET) alterations are present in up to 60% of non-small cell lung cancer and are associated with a poor prognosis. Capmatinib and tepotinib are currently the only two approved targeted therapies by the U.S. Food and Drug Administration (FDA) for patients with MET exon 14 skipping mutation. Several agents are being developed to tackle an unmet need in patients with MET alterations. Some of these agents are being used in combination with EGFR targeted therapy to mitigate resistance to EGFR inhibitor. These agents are poised to provide new hope for these patients.
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Antineoplásicos , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Mutação , Proteínas Proto-Oncogênicas c-met , Humanos , Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Terapia de Alvo Molecular/métodos , Medicina de Precisão/métodos , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas Proto-Oncogênicas c-met/genética , Proteínas Proto-Oncogênicas c-met/antagonistas & inibidoresRESUMO
In recent years, cancer has become one of the primary causes of mortality, approximately 10 million deaths worldwide each year. The most advanced, chimeric antigen receptor (CAR) T cell immunotherapy has turned out as a promising treatment for cancer. CAR-T cell therapy involves the genetic modification of T cells obtained from the patient's blood, and infusion back to the patients. CAR-T cell immunotherapy has led to a significant improvement in the remission rates of hematological cancers. CAR-T cell therapy presently limited to hematological cancers, there are ongoing efforts to develop additional CAR constructs such as bispecific CAR, tandem CAR, inhibitory CAR, combined antigens, CRISPR gene-editing, and nanoparticle delivery. With these advancements, CAR-T cell therapy holds promise concerning potential to improve upon traditional cancer treatments such as chemotherapy and radiation while reducing associated toxicities. This review covers recent advances and advantages of CAR-T cell immunotherapy.
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Imunoterapia Adotiva , Neoplasias , Receptores de Antígenos Quiméricos , Humanos , Imunoterapia Adotiva/métodos , Receptores de Antígenos Quiméricos/uso terapêutico , Receptores de Antígenos Quiméricos/imunologia , Neoplasias/terapia , Neoplasias/imunologia , Neoplasias Hematológicas/terapia , Edição de Genes/métodos , Linfócitos T/imunologia , Linfócitos T/transplanteRESUMO
BACKGROUND & AIMS: Obesity and non-alcoholic fatty liver disease (NAFLD) are known risk factors for gastrointestinal (GI) cancers. However, GI carcinogenesis in lean NAFLD patients remains unclear. This systematic review and meta-analysis aims to investigate the association between lean NAFLD and GI cancer risk. METHODS: PubMed, Embase and Cochrane Library databases were systematically searched (from inception date to April 2023) for cohort studies assessing GI cancers in lean (body mass index [BMI] < 25 kg/m2 or < 23 kg/m2 in Asians) and non-lean (BMI ≥25 kg/m2 or ≥ 23 kg/m2 in Asians) NAFLD individuals. Data from eligible studies were extracted, and meta-analysis was carried out using a random effects model to obtain risk ratios (RRs) with 95% confidence intervals (CIs). Subgroup analyses, meta-regressions and sensitivity analyses were also performed. This study was registered in PROSPERO (CRD42023420902). RESULTS: Eight studies with 56,745 NAFLD individuals (11% were lean) and 704 cases of incident GI cancers were included. Lean NAFLD was associated with higher risk of hepatic (RR 1.77, 95% CI 1.15-2.73), pancreatic (RR 1.97, 95% CI 1.01-3.86) and colorectal cancers (RR 1.53, 95% CI 1.12-2.09), compared to non-lean NAFLD. No significant differences were observed for oesophagus, gastric, biliary and small intestine cancers. CONCLUSIONS: This study shows that lean NAFLD patients have an increased risk of liver, pancreatic and colorectal cancers compared to non-lean NAFLD patients, emphasizing the need to explore tailored cancer prevention strategies for this specific patient group. Further research is required to explore the mechanisms underlying the association between lean NAFLD and specific GI cancers.
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Neoplasias Colorretais , Neoplasias Gastrointestinais , Hepatopatia Gordurosa não Alcoólica , Humanos , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Fatores de Risco , Neoplasias Gastrointestinais/epidemiologia , Neoplasias Gastrointestinais/complicações , Neoplasias Colorretais/complicaçõesRESUMO
Introduction: The increasing cancer incidence and mortality rates in Costa Rica have become a public health concern, with prostate, breast, and colorectal cancers being the most prevalent. This study aimed to analyze the trends in cancer incidence and mortality rates by tumor type, sex, age group, and geographic region using data from the Costa Rican National Cancer Registry. Methods: In this retrospective study, we analyzed cancer incidence and mortality anonymized data from the Costa Rican National Cancer Registry between 2010 and 2020. The study included data on cancer cases diagnosed and deaths attributable to cancer within the population. Results: Our findings revealed variations in cancer incidence and mortality rates based on geographic region, age group, and tumor type. Cancer was most predominant in the province of San Jose, followed by Alajuela, Heredia, Cartago, Guanacaste, and Puntarenas. Breast cancer, colorectal cancer, and prostate cancer were the leading causes of cancer in both sexes. Mortality rates due to gastric cancer and prostate cancer were highest among men, while breast cancer was the leading cause of cancer mortality among women. Conclusion: The results of this study underscore the need for targeted prevention and screening programs, improved access to treatment for patients living in rural areas, and a comprehensive cancer control program in Costa Rica. By implementing evidence-based interventions, such as tobacco control programs, cancer screening initiatives, and equitable access to cancer treatment, the cancer burden in Costa Rica can be mitigated, ultimately improving the overall health of the population.
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Molecular and cellular components of the tumor microenvironment are essential for cancer progression. The cellular element comprises cancer cells and heterogeneous populations of non-cancer cells that satisfy tumor needs. Immune, vascular, and mesenchymal cells provide the necessary factors to feed the tumor mass, promote its development, and favor the spread of cancer cells from the primary site to adjacent and distant anatomical sites. Cancer-associated fibroblasts (CAFs) are mesenchymal cells that promote carcinogenesis and progression of various malignant neoplasms. CAFs act through the secretion of metalloproteinases, growth factors, cytokines, mitochondrial DNA, and non-coding RNAs, among other molecules. Over the last few years, the evidence on the leading role of CAFs in gynecological cancers has notably increased, placing them as the cornerstone of neoplastic processes. In this review, the recently reported findings regarding the promoting role that CAFs play in gynecological cancers, their potential use as therapeutic targets, and the new evidence suggesting that they could act as tumor suppressors are analyzed and discussed.
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The tyrosine kinase Fyn is a member of the SRC family of kinases, and its sustained activation is closely linked to tumor cell migration, proliferation, and cell metabolism. Recently, Fyn has been found to be expressed in various tumor tissues, and the expression and function of Fyn vary between tumors, with Fyn acting as an oncogene to promote proliferation and metastasis in some tumors. This article summarizes the recent studies on the role of Fyn in different human tumors, focusing on the role of Fyn in melanoma, breast cancer, glioma, lung cancer, and peripheral T-cell lymphoma in order to provide a basis for future research and targeted therapy in different human tumors.
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Melanoma , Proteínas Tirosina Quinases , Humanos , Fosforilação , Proteínas Proto-Oncogênicas c-fyn/genética , Proteínas Proto-Oncogênicas c-fyn/metabolismoRESUMO
Among the different immune cells present within tumors, B cells also infiltrate human papillomavirus-positive (HPV+) oropharyngeal tumors. However, the role of B cells during programmed death-1 (PD-1) blockade in HPV+ oropharyngeal cancer needs to be better defined. By using the preclinical mouse model for HPV+ oropharyngeal cancer (named mEER), we characterized B cells within tumors and determined their functional role in vivo during PD-1 blockade. We determined that treatment naïve tongue-implanted tumors, which we have previously demonstrated to be sensitive to PD-1 blockade, contained high infiltration of CD8+ T cells and low infiltration of B cells whereas flank-implanted tumors, which are resistant to PD-1 blockade, contain a higher frequency of B cells compared to T cells. Moreover, B cell-deficient mice (µMt) and B cell-depleted mice showed a slower tumor growth rate compared to wild-type (WT) mice, and B cell deficiency increased CD8+ T cell infiltration in tumors. When we compared tongue tumor-bearing mice treated with anti-PD-1, we observed that tumors that responded to the therapy contained more T cells and B cells than the ones that did not respond. However, µMt mice treated with PD-1 blockade showed similar tumor growth rates to WT mice. Our data suggest that in untreated mice, B cells have a more pro-tumorigenic phenotype potentially affecting T cell infiltration in the tumors. In contrast, B cells are dispensable for PD-1 blockade efficacy. Mechanistic studies are needed to identify novel targets to promote the anti-tumorigenic function and/or suppress the immunosuppressive function of B cells in HPV+ oropharyngeal cancer.
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Biliary tract cancers (BTCs) are a rare pathology and can be divided into four major subgroups: intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, hilar cholangiocarcinoma, and gallbladder cancer. In the era of precision oncology, the development of next-generation sequencing (NGS) allowed a better understanding of molecular differences between these subgroups. Thus, the development of drugs that can target these alterations and inhibit the abnormal pathway activation has changed the prognosis of BTC patients. Additionally, the development of immune checkpoint inhibitors and a better understanding of tumor immunogenicity led to the development of clinical trials with immunotherapy for this scenario. The development of biomarkers that can predict how the immune system acts against the tumor cells, and which patients benefit from this activation, are urgently needed. Here, we review the most recent data regarding targeted treatment and immunotherapy in the scenario of BTC treatment, while also discussing the future perspectives for this challenging disease.
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OBJECTIVES: This study investigated the impact of cancer diagnosis status, individual feelings of preparedness, and other covariates on objective emergency preparedness among women diagnosed with gynecological cancers before or after the 2017 Hurricanes Irma and Maria in Puerto Rico. METHODS: This study included 240 women who were interviewed by telephone from 9/2019-11/2020. Objective emergency preparedness was assessed using a list of six items. Subjective emergency preparedness was assessed by asking the women how prepared they felt (well, somewhat, or not at all) to face an emergency. Crude and multivariable logistic regression analyses were conducted to assess the associations (odds ratios [ORs] and 95% confidence intervals [CIs]) between variables of interest and objective preparedness. RESULTS: Before and after the hurricanes, 60% and 66% of women, respectively, were objectively prepared. Before the hurricanes, women reporting feeling well-prepared (vs. not prepared) (OR=9.31, 95%CI:3.96-21.91) and those who were diagnosed before (vs. after) the hurricanes (OR=1.71, 95%CI:0.95-3.09) were more likely to be objectively prepared. After the hurricanes, self-perceived well-preparedness (OR=2.46, 95% CI: 1.10-5.51) was positively associated with emergency preparedness when compared to feeling unprepared. CONCLUSIONS: Perceptions of emergency preparedness and having a cancer diagnosis increased the likelihood of being objectively prepared for an emergency. POLICY SUMMARY: This study demonstrates the need for state, territorial, and federal governments to include emergency preparedness plans for cancer patients in the Comprehensive Cancer Control plans. The study also indicates a need for cancer specific emergency preparedness information to be readily available for patients.
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Defesa Civil , Tempestades Ciclônicas , Neoplasias , Humanos , Feminino , Porto Rico/epidemiologia , EmoçõesRESUMO
The overall burden of cancer is rapidly increasing worldwide, reflecting not only population growth and aging, but also the prevalence and spread of risk factors. Gastrointestinal (GI) cancers, including stomach, liver, esophageal, pancreatic, and colorectal cancers, represent more than a quarter of all cancers. While smoking and alcohol use are the risk factors most commonly associated with cancer development, a growing consensus also includes dietary habits as relevant risk factors for GI cancers. Current evidence suggests that socioeconomic development results in several lifestyle modifications, including shifts in dietary habits from local traditional diets to less-healthy Western diets. Moreover, recent data indicate that increased production and consumption of processed foods underlies the current pandemics of obesity and related metabolic disorders, which are directly or indirectly associated with the emergence of various chronic noncommunicable conditions and GI cancers. However, environmental changes are not restricted to dietary patterns, and unhealthy behavioral features should be analyzed with a holistic view of lifestyle. In this review, we discussed the epidemiological aspects, gut dysbiosis, and cellular and molecular characteristics of GI cancers and explored the impact of unhealthy behaviors, diet, and physical activity on developing GI cancers in the context of progressive societal changes.
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Dieta , Neoplasias Gastrointestinais , Humanos , Fatores de Risco , Obesidade , Estilo de VidaRESUMO
Gynecologic cancers are reproductive disorders characterized by pelvic pain and infertility. The identification of new predictive markers and therapeutic targets for the treatment of gynecologic cancers is urgently necessary. One of the recent successes in gynecologic cancers research is identifying the role of signaling pathways in the pathogenesis of the disease. Recent experiments showed long noncoding RNAs (lncRNA) can be novel therapeutic approaches for the diagnosis and treatment of gynecologic cancers. LncRNA are transcribed RNA molecules that play pivotal roles in multiple biological processes by regulating the different steps of gene expression. Metastasis-associated lung adenocarcinoma transcript-1 (MALAT1) is a well-known lncRNA that plays functional roles in gene expression, RNA processing, and epigenetic regulation. High expression of MALAT1 is closely related to numerous human diseases. It is generally believed that MALAT1 expression is associated with cancer cell growth, autophagy, invasion, and metastasis. MALAT1 by targeting multiple signaling pathways and microRNAs (miRNAs) could contribute to the pathogenesis of gynecologic cancers. In this review, we will summarize functional roles of MALAT1 in the most common gynecologic cancers, including endometrium, breast, ovary, and cervix.
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Adenocarcinoma , Neoplasias dos Genitais Femininos , Neoplasias Pulmonares , MicroRNAs , RNA Longo não Codificante , Humanos , Feminino , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Epigênese Genética , MicroRNAs/genética , MicroRNAs/metabolismo , Neoplasias Pulmonares/genética , Adenocarcinoma/genética , Neoplasias dos Genitais Femininos/genética , Regulação Neoplásica da Expressão Gênica , Proliferação de Células/genéticaRESUMO
BACKGROUND: Triple-positive breast cancer (TPBC) is a tumor that simultaneously expresses estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2). Luminal A-like TPBC is a special subtype with a favorable prognosis but benefits less from HER2-targeted therapy. However, little is known about how to identify luminal A-like TPBCs. Therefore, our study aims to explore a clinically feasible method to identify luminal A-like TPBCs using immunohistochemical (IHC) markers. METHODS: Our cohort enrolled consecutive 190 patients with early-stage TPBCs diagnosed, treated and followed up in our hospital between 2013 and 2019. Patients whose IHC staining displayed ≥ 50% in both ER and PR scores and B-cell lymphoma 2 (BCL2) positivity were classified as cohort A (n = 64), and the rest were enrolled in cohort B (n = 126). Kaplan-Meier plotter and log-rank test were used to compare the survival difference between cohort A and cohort B and the efficacy of trastuzumab therapy in the two cohorts. RESULTS: The disease-free survival (DFS) of patients in cohort A was significantly better than in cohort B (p = 0.031). In cohort A, there was no statistically significant difference in DFS between patients treated with trastuzumab and those without trastuzumab (p = 0.663). While in cohort B, patients treated with trastuzumab had significantly better DFS than those without trastuzumab (p = 0.032). Multivariate survival analysis showed that cohort A was associated with better DFS(95%CI 1.046-11.776, p = 0.042). CONCLUSION: TPBCs consist of heterogeneous subtypes. Detecting the expression of ER, PR and BCL2 via IHC can help identify luminal A-like TPBCs. This study will enable individualized treatment of TPBCs.