Purpose: The benefits of Physical Activity (PA) considered as a major supportive care in cancer patients, on survival, and recurrence risk is largely disseminated in public communication. However, these data must be taken with caution. The main objectives were to review the evidence and limits of studies reported regarding the post-diagnosis PA role on cancer survival and recurrence risk to secondly discuss of research perspectives on PA programs.
Method: The narrative review included all published or ongoing studies in English during the last 20 years related to PA, survival and recurrence risk with a systematic search on main databases.
Results and discussion: The current evidences regarding the PA role on survival and recurrence risk were only based on cohort studies, mainly in breast cancer. The major methodological limits identified as the lack of PA change assessment, PA level assessed largely by self-reported methods and the significant inter- but also intra- variability make the interpretation of data very. Beyond the use of rigorous RCT, the major issue is to develop adapted and personalized interventions to progressively increase PA level overtime in cancer survivors.
Conclusion: Despite the lack of causal relationship between post-diagnosis PA, survival and recurrence risk, the review underlines several interesting research perspectives. The future PA interventions, using innovative tools and integrated to the “real-life” will argued for the potential antitumoral PA role growing in literature.
With the discovery by Calghatgi (2013) that three common antibiotics (Abs) increased mitochondrial reactive oxygen (ROS) and lipid peroxide (LP) and depleted their natural absorbant glutathione led me to investigate further the potential impacts of these genotoxic substances on carcinogenesis. The range of impacts on mitochondria and cellular DNA varied by antibiotic to those consistent with known prior contributions to carcinogenesis. Specific cancers probably increased by these changes were HCC, RCC (KCC), CRC, cancer of the esophagus. Tumor suppressor gene mutations resulting from LP were noteworthy in this regard and mutations induced in CRC were consistent with those found in carcinogenesis of CRC. In addition depression of short chain fatty acids in microbiomes were found which depress the immune system increasing risk of all cancers. Many cancers were increased according to epidemiological studies linking Abs with elevated odds ratios, with one concern in particular, fatal breast cancer. The impact of loss of functionality of the mitochondria was also linked to depression of the citric acid cycle and therefore ATP which deflected metabolism to glycolysis, the Warburg mechanism also increasing risk of all cancers, favoured by cancer cells. In conclusion, some portion of many cancer types are probably increased in likelihood by number, type and frequency of Abs treatment and chronic residue exposure which varies from individual to individual. This led me to propose a three pronged carcinogenesis mechanism for Abs. 1. Cancer critical mutations 2. Immune depression 3. loss of mitochondrial functionality leading to Warburg effects. Damage to mitochondria were also noted by common pesticides tested in China and cancer associations were also found for many pesticides supporting a similar contributory etiology. Heart health concerns were raised by these findings because of the myriad mitochondria in the heart and because of long term reliability needs. Studies suggesting hearts were affected by Abs and pesticide exposure were presented. Because of their geographical ubiquitousness and the huge range of diseases associated with mitochondrial dysfunction, antibiotics and pesticides and bacteriocidal biocides are of concern for biodiversity and life in general. I propose research steps to evaluate Abs safety and suggest directions for further research and make suggestions on ways to ameliorate Abs toxicity.
The main goal of hyperthermia is to elevate the tumor temperature to kill tumor cells and improve local control. The usage of hyperthermia is combination with radiotherapy or chemotherapy. Hyperthermia is delivered in different types of cancers like breast cancer, melanoma and sarcoma. Breast cancer treatment enroll surgery, chemotherapy, radiotherapy and hormone therapy. Hyperthermia is given once or twice a week concomitantly with radiotherapy or chemotherapy. This short review will enlight the types, physics, and the results of hyperthermia especially in the management of breast cancer therapy.
Breast cancer is a complex disease and one of the main causes of cancer-related mortality in women worldwide. In case of approximately 15% of all breast cancers, three markers i.e. estrogen receptors (ER), progesterone receptors (PR) and human epidermal growth factor receptors-2 (HER2) are not expressed, and is commonly termed as triple-negative breast cancer (TNBC). Particularly, TNBC is associated with a higher percentage of breast cancer related mortality, which is often aggressive and most frequently found with a BRCA1 mutation or increased basal marker expression. However, due to the limitations of chemotherapy and radiation based treatment; the current challenge is to establish a new strategy of diagnosis and treatment of TNBC. The deregulation of a number of microRNAs (miRNAs) in breast cancer has been widely reported. Therefore, this review is directed towards enhancing our understanding of the involvement of various miRNAs in the pathology of TNBC, their upregulations and downregulations and the effects on various factors. From recent studies a number of miRNAs are found to be related with TNBC, which have great potential to be used as a biomarker to determine the disease prognosis and predict the fate of disease. Again miRNA can be targeted to be applied as a therapeutic to provide a great benefit to the patients of TNBC by finding a new, safe, and effective treatment strategy.
Background: Breast cancer (BC) is one of the most prevalent malignancies. BC survivors have higher risk of second primary cancers than the general population. There is an increased interest in BC survivor management, including the prevention of these second cancers. The aim of this study was to assess the risk of gynaecological malignancy (GM) as second neoplasm among BC patients in our population.
Methods: Patients with invasive BC diagnosed from 1980 to 2014 included in the Girona Cancer Registry were included. The incidence of second GM in these patients was compared to those in the general population. Second primary cancer was stated as a tumour diagnosed after 2 months from the BC diagnosis. Standardized incidence ratios (SIR) and absolute excess of risk (AER) were calculated.
Results: 9,717 patients were diagnosed with invasive BC during this period, with a median age at diagnosis of 61 years, and a median follow-up of 7.9 years. 117 of them developed a second GM. By tumour type, the only statistically significant higher SIR was observed for corpus uteri cancer (SIR:2.28 95% CI 1.82-2.83; AER:6.43 95% CI 4.13-9.14). After reviewing the histology of the corpus uteri cancer cases, we found that 71.4% were type I (endometrioid adenocarcinoma), 15.5% type II (serous adenocarcinomas and clear cell carcinomas), 10.7% carcinosarcomas, 2.4% sarcomas and there were no unspecified malignant neoplasms.
Conclusion: BC survivors have an increased risk of corpus uteri cancer, with an increase in unfavourable histologies compared to the general population. Lifelong primary and secondary prevention interventions should be recommended for these patients.
Breast cancer is the most common cancer in women and is a major public health problem. It is divided into several subtypes, including triple negatives. The general objective of our study is to establish the profile and the management of patients with triple negative breast cancer over a period of 2 years, operated in our department.
During our study period, triple-negative breast cancers accounted for 10% of our population. The most affected age group ranges from 50 to 60. The majority of patients in our sample are pauciparous. In the group of patients who received hormone therapy, it was mainly HRT for 4 to 6 years. 96.77% of patients consulted a health worker within 3 months of the discovery of the signs. Adenopathies are frequently present at the time of diagnosis. 93.54% of the cases have an invasive ductal carcinoma. Triple negative cancers are essentially poorly differentiated. Triple-negative cancer has a high rate of cell renewal. In our study, neoadjuvant chemotherapy is mostly indicated for triple-negative breast cancers ≥ 30 mm at diagnosis and a delayed lumpectomy is then performed in 23.52% of the patients. For tumors of < 30 mm size, a lumpectomy is performed immediately in 76.47% of the patients, followed by adjuvant chemotherapy.
Mastectomy was performed in 45.16% of patients; it was mainly indicated in front of a large tumor size associated with a small breast volume, then multifocal breast tumors. Breast reconstruction was performed in 21.42%. Radiation therapy is indicated in the majority of patients, postoperatively. In our population, 11 patients were proposed to have an oncogenetic survey; it was mainly indicated based on the Manchester criteria in front of a young age and a family history of cancer. There are two BRCA 1 mutations, one BRCA 2 mutation, and one case of absence of mutation. The therapeutic intake in case of a mutation is directed towards a prophylactic bilateral mastectomy and adnexectomy, proposed at the age of 40. Two patients had presented triple negative recurrences of their already treated breast cancer; first case PDL1 positive PD-L1 ≥ 1% treated with immunotherapy combined with chemotherapy (atezolizumab/abraxane) while the second and second PDL1 negative treated with chemotherapy alone.
Despite their low frequency, triple negative breast cancers represent a subgroup marked by pejorative characteristics, a reserved prognosis, with limited treatment options.
Rosai-Dorfman disease (RDD) is an idiopathic, benign proliferation of histiocytes that can be present in multiple organs such as lymph node, skin, soft tissue, orbit, central nerve system and bone; however, it rarely occurs in the breast. In general, RDD is a painless, firm and poorly defined lesion, which can radiologically mimic a breast cancer and is therefore an important differential consideration. The diagnosis of breast RDD is challenging, especially on a small biopsy specimen. We report a unique case of breast RDD with a literature review including common presentation, differential diagnosis, and recommended management. A high index of suspicion for this rare entity is essential to render a correct diagnosis, thereby avoiding unnecessary diagnostic tests and treatment.
The study aimed to identify possible environmental risk factors for breast cancer among women in Gaza Strip and conducted in 2010. A case- control study design was used with face to face interviews by structured questionnaire with breast cancer patient women as well as healthy women. Statistical Package of Social Science (SPSS) was used to analyze the collected data. The study population was 288 women, 144 were women with breast cancer (cases) and 144 were healthy women (controls) with response rate 100% for cases as well as controls. The study was carried out in the two main hospitals in Gaza Strip (El-Shifa and European Gaza) and on cases who had a regular follow up in each hospital, while controls have been chosen from women who had no history of breast cancer by mammogram or by self-examination. In this study the main statistically significant risk factors were; marital status, educational status, physical trauma on breast, medication for infertility treatment, eating red meat 500g or more weekly, eating canned food, eating chicken skin, eating raw and cooked vegetables, using oils with saturated fats in cooking, living in or beside a farm, dealing with crops with naked hands, working in a farm during pesticides application or during 24 hours of pesticides application, cleaning pesticides’ equipment, living with people working in a farm or a agricultural field, and application of pesticides personally. In contrary, no statistically significant differences were found between cases and controls in relation to area of residency, exposure to X-ray in the past, having radiation therapy, getting contraceptive pills, using hair dyes, using anti-deodorant underarm, using facial cosmetics, using hair removal ointment, washing vegetables and fruits, buying and transporting pesticides, and wearing protective tools during pesticides mixing and application.
When a woman consults a doctor about Hormone Replacement Therapy (HRT), the first concern is that there is an increased risk of breast cancer with HRT. And this sole reason might be the reason for refusing the offer of HRT. However, this practice has minimal basis and evidence to support it. Although HRT is an umbrella term, women who have no uterus receive oestrogen-only HRT or Estrogen Replacement therapy (ERT). No valid study has linked ERT with an increased risk of breast cancer [1,2].
The presence of an incidental finding, defined as an abnormality which is unrelated to the initial scanning indication, is widely increases due to the access to new devices and imaging modalities. This growing number of incidental findings can lead to additional medical care including unnecessary tests nevertheless, in a minority of patients, can lead to diagnosis of an important and unexpected condition that could be crucial for the patient. We reported three cases in which nuclear medicine imaging, performed for different reasons and showed a relevant and unexpected pathology. In the case 1, a bone scan, performed in a 66 aged woman for breast cancer staging, allowed the diagnosis of a uterine fibroma. In the case 2, a HMPAO labeled-WBC scintigraphy performed because of a suspect of osteomyelitis, showed a remarkable heart-shaped photopenic area, highly suggestive of cardiac global dilatation. In the case 3, a 62 aged man referred to bone scintigraphy for the staging of recent diagnosed lung cancer. The bone scan allowed the diagnosis of a meningioma. Therefore, the occurrence of incidental findings could lead to reveal relevant abnormalities for the diagnostic pathway.
Background: In this study, we aimed to investigate the role of prognostic factors on breast cancer survival in Iran.
Methods: This study was carried out using data from 500 participants with breast cancer. Data were gathered from medical records of patients referring to four breast cancer research centers in Esfahan, Iran, between 1990 – 2000. Age at diagnosis (year), size of tumor, Involve lymph nodes, tumor grade, and family history and married were the prognosis factors considered in this study. A Cox model was used.
Results: The median follow-up period was 29.71 months with the interquartile range of 19-61 months. During the follow-up period, 57 (10%) patients died from breast. The Cox model showed that number of lymph nodes involved, and the tumor size and grade tumor are the prognostic factors survival in breast cancer.
Conclusion: This study, confirmed the importance of early diagnosis of cancer before the involvement of lymph nodes and timely treatment could lead to longer life and increased quality of life for patients.
Objective: The liver is the second most common site of distant metastases from breast cancer. We investigated the risk factor liver metastasis in patients with breast cancer.
Methods: We studied Age, Menopausal status, Histologic Type, Tumor size, Number of cancerous axillary lymph nodes, in two groups with liver metastases with logistic regression to identify independent liver metastasis risk factors in breast cancer patients.
Results: Age, menopausal status, number of cancerous axillary lymph nodes and tumor size are the independent risk factors liver metastases in patients with breast cancer.
Conclusion: The increase number of cancerous axillary lymph nodes and tumor size may be diagnostic markers for liver metastases from breast cancer.
Obesity is a chronic and metabolic disease with a high increasing prevalence worldwide. It has multifactorial pathogenesis including genetic and behavioral factors [1-5]. Overweight and obesity have been defined and classified by the World Health Organization (WHO) and the National Institutes of Health (NIH) [2,3]. A person with a normal weight has Body Mass Index (BMI) of 18.5-24.9. A person with a BMI under 18.5 is called underweight. An adult having a BMI of 25-29.9 is overweight and pre-obese. Class 1 obesity is defined as a BMI between 30.00-34.99. Class 2 (Severe) Obesity is to have a BMI between 35.00-39.99. Morbid (Extreme, Class 3) obesity is to have a BMI over 40 [1-5]. Obesity is significantly associated with enhanced morbidity and mortality rates. It has also various economic, medical and psychological effects and causes health problems including many systemic diseases, economic costs and burdens, social and occupational stigmatization and discrimination and productivity loss [4-6]. Obesity carries the increased risk of development of many systemic and chronic diseases, including sleep apnea, depression, insulin resistance, Type 2 (adult-onset) diabetes, Gout and related arthritis, degenerative arthritis, hypertension, dyslipidemia, heart disease such as myocardial infarction, congestive heart failure, or coronary artery disease, polycystic ovary syndrome and reproductive disorders, Pickwickian syndrome (obesity, red face and hypoventilation), metabolic syndrome, non-alcoholic fatty liver disease, cholecystitis, cerebrovascular accident, colonic and renal cancer, rectal and prostatic cancer in males, and gallbladder, uterus and breast cancer in females [6-12].
In recent years, some publications reported that obesity has been strongly associated with some ocular diseases including age-related cataract and maculopathy, glaucoma, and diabetic retinopathy [13-16].
The recent reports demonstrated that the central corneal thickness and intraocular pressure were increased while as mean thickness of RNFL and retinal ganglion cell and choroidal thickness (CT) were decreased in the morbidly obese subjects [17-19]. However, another study has reported that CT increased in obese children . On the other hand, a recent study reported that all values of the specific tests used to evaluate the ocular surface were within the normal range . In some experimental studies, it has been demonstrated that obesity may cause retinal degeneration [22,23]. Additionally, in a past meeting presentation, it has been speculated that keratoconus is associated with severe obesity . Teorically, idiopathic intracranial hypertension, and papilledema may also be associated with obesity . Obesity may be also a cause of mechanical eyelid abnormalities such as entropion . However, further investigations are needed to detect the significant relationship between these diseases and obesity.
On the other hand, the ocular surgeries of obese patients are difficult compared to normal weight-subjects. The posterior capsule rupture and vitreous loss may easily develop during cataract surgery of these patients because obese patients have an elevated vitreous pressure and operating table cannot often be lowered or surgeon’s chair cannot be elevated sufficiently to provide the clear viewing of the operating area and tissues. So, some different surgical manipulations such as standing phacoemulsification technique and reverse Trendelenburg position have been developed. Additionally, the standing vitrectomy technique has been used for vitreoretinal interventions in morbidly obese patients [27,28].
In conclusion, all obese subjects should be subjected to a completed ophthalmological examination and to relevant clinics for the detection of possible comorbidities and diseases
German surgeon, Vincenz Czerny, transplanted a patient’s own lipoma located in the hip to it’s breast after gland excision due to mastitis in 1895. Dr. Vincenza reported that for at least a year he didnt observe any problem on the operated breast . Injection of adipose tissue to the breast has been used in breast cancer patients during breast reconstruction and lumpectomy. And in cases of revision autologous tissues are used for reconstruction. In clinical practice, many breast cancer patients apply to the clinics mostly after radiotherapy for reconstruction. Rigotti et al used purified autologous lipoaspirates in breast cancer patients with late term complications of radiation therapy and observed increase in neovascularization and wound healing . Panettiere and colleagues compared aesthetic and functional features of fat grafts in radiotherapy received breast cancer patients and control group. In the fat graft group, all clinical symptoms and aesthetic scores were significantly higher than the control group .
In plastic surgery especially after the surgical treatment of breast cancer, prosthetic techniques, various autologous flaps or combinations of both are performed for breast reconstruction. Particularly breast reconstructions following adjuvant radiotherapy have less success rates due to adverse effects of radiotherapy [4-10]. There are reports showing reduced complications rates with use of fat grafts before and after breast reconstruction with prosthesis in patients received radiotherapy after lumpectomy or mastectomy.
With that, in patients receiving radiotherapy after fat grafting, local complications such as fat necrosis, infection can be seen more [3,11]. It was reported that adipocytes may had paracrine and endocrine interactions with tumor cells and stromal elements . The fat grafts used in breast cancer were thought to cause local recurrence, distant metastasis or development of new cancers; there was no relationship in the clinical series. There is aromatase activity in the adipose tissue. Thus, fat tissue is the main source of post-menopausal estrogen hormone. Tumor cells and surrounding tissue were found to be higher in aromatase activity. Therefore, when fat tissue is injected subcutaneous or under the gland rather than into the parenchyma local recurrence risk is low .
When fat tissue is injected to breast, a good physical examination and mammography should be performed. After fat injection, sometimes calcifications are formed as a result of undergoing necrosis and they interfere with malignancy. Therefore before and after the procedure, mammography must be taken for comparison and existing and or newly developed calcifications should be determined.
According to literature, about 90% of death from cancer is related to metastasis. Metastatic process present many similarity to some other biological processes. Once we have examined some relevant biomedical literature, by understanding the real causes of metastasis, it would become much more possible to introduce new therapeutic strategies to delay or in some cases even to stop this kind of killer process. Breast cancer, as an example, produces metastasis to different organs, which seems to be related to the subtype. We believe that a deep understanding of the roles of breast cancer cells and their interactions with the liver microenvironment in early breast cancer metastasis could be a crucial factor for the design and development of effective BCLM breast cancer liver metastases therapeutic strategies and to better understand the general process. Let’s suppose the secondary organ or organs can be considered as incubator/s for the primary metastatic cells. What kind of consequences we can have in therapy field if there is an active regulating role in determining the location of secondary cancers?
Let’s observe the role played by liver, bone marrow, CNS central nervous system, lungs, lymphocytes and other secondary locations/organs a little bit closer or maybe from a different angle let’s suppose we try to come up with just a hypothesis. Just let’s take this as a possibility, and we take the thread to see where it takes us.
Broad-spectrum sunscreens are now widely used worldwide as an adjunct to help prevent sunburn, skin cancers and premature skin aging. In the United States, all persons older than 6 months are recommended to apply sunscreen to all sun-exposed skin from toes to head except eyes and mouth even on cloudy days. Such a recommendation is apparently based on concepts that exposure to sunlight damages the skin, the damage is cumulative and hence any sun exposure should be minimized or prevented. This communication raises several questions suggesting that the above recommendation may need to be reconsidered. For example, numerous previous studies have indicated many potential health benefits from non-burning sun exposure including protection against sunburn, melanoma, colorectal cancer, breast cancer and prostate cancer, increasing vitamin D synthesis, helping sleep, reducing blood pressure, heart attack and stroke. Recent studies suggested that regular lifetime non-burning sun exposure may not result in premature skin aging and the skin aging is mainly caused by the intrinsic factor. Skin aging or whole-body aging has been recently postulated to be mainly attributed to a gradual reduction in cardiac output/index with age and a new anti-aging or age-reversing nutritional theory has been proposed. An apparent lack of long-term cumulative sunray damage was also supported by reported age independence in incidences of sunburn and skin cancers. It is of interest that the current US policy is different from that of World Health Organization and Australia recommending the need of sun protection only when UV Index is 3 or greater. In view of the above, some general guidelines regarding when to best apply sunscreen are proposed.
Introduction: Cancer treatment and prognosis depend heavily on early detection. Survival in the early stages is excellent for almost all types of cancer. Unfortunately, in Saudi Arabia, a large number of cancer patients present with advanced disease, resulting in a poor prognosis. There are three levels of delay in the management of cancer patients. The first level is the time between the first cancer-related symptoms and the presentation to the health facility, the second level is from the presentation to the diagnosis, and the third level is between the diagnosis and the treatment. This study aims to determine if there is a delay, at what level and to study the factors causing such delays.Materials and methods: Two hundred cancer patients who presented to the Armed Forces Hospital Southern Region, Oncology Department, were interviewed from January 1st to June 30th, 2018. The interviews were conducted by trained physicians familiar with the questionnaire’s contents. The questionnaire consisted of four sections: a demographic section and three more sections to identify factors causing the delay at the three levels from the patients’ perspectives. All data were analyzed using the SPSS version 20.0.Results: The mean patient age was 63 years. A total of 112 patients were female and 88 were male. The most common cancer type was breast cancer (27.5%). Among the patients, 61% were illiterate and 25.5% had elementary school degrees, 86% expressed little or no general medical knowledge about cancer. More women than men paid attention to cancer symptoms (70% vs. 54%). 75% of the patients presented to the first health facility after 2 months from the first appearance of symptoms (level 1 delay). Only 2% of the patients presented within one week. 50% of the patients received a diagnosis after visiting two health facilities. All patients were diagnosed at hospitals. 40% of patients used alternative medicines, 70% of whom thought this was the cause of their delayed presentations. 67% had their diagnosis confirmed within one month (level 2 delay), and 66% started their definitive treatment within one month (level 3 delay). 75% of the patients blame themselves for the delay. Educational level (p = 0.03), knowledge about cancer (p < 0.01), and the use of complementary and alternative medicines (CAM) (p = 0.01) were significantly associated with delayed presentation of patients to the health facility. Conclusion: There is a delay in the presentation of cancer patients (level 1) in the southern part of Saudi Arabia. Educational level, knowledge of cancer symptoms, and use of complementary and alternative medicines are the main causes. There were no delays in diagnosis and start of treatment (level 2,3).
Background: Breast self-examination is the most important screening method for early detection and diagnosis of Breast cancer. Females assess their breasts regularly to detect any abnormalities to seek instant medical attention. Objectives: The main objective of the study was to assess the knowledge on breast self-examination among female adolescents of Nepal.Method: A cross-sectional study was conducted using self-structured questionnaires among female adolescents of Model Multiple College, Dhanusha. The sample size was 120 participants. Probability proportionate stratified sampling technique was used to collect the data from October 28th to November 12th, 2013. Data were processed through Statistical Package for Social Sciences version 16 and analyzed using descriptive statistics.Results: Out of 120 participants 67.5% participants had knowledge about breast cancer and 40% had knowledge of breast self-examination (BSE). Most of them (94.2%) had a poor knowledge of BSE followed by 5.8% of participants with a moderate level of knowledge of BSE. The mean knowledge score was 18.7 ± 3.5. The majority (66.7%) of participants were from science faculties. More than half (51.7%) of participants stated source of information on BSE was health personnel. Only 25% of the respondent had a family history of breast cancer. Conclusion: The study revealed that most (94.2%) of the participants had poor knowledge of breast self-examination. There is further need for awareness and health education on breast self-examination.
Cancer metastasis to the pituitary gland is rare, but in most cases, it originates from a late-stage breast tumor or lung cancer. The most common symptoms of metastasis to the pituitary gland are diabetes insipidus and visual disturbance. The common site of metastasis is the posterior portion of the pituitary gland because it is highly vascularized. Metastases to this site represent 1% of all tumors . Metastasis to the pituitary gland is difficult to diagnose by hormonal analysis and magnetic resonance imaging of the brain and requires biopsy for confirmation .
Genome-wide association studies (GWAS) have uncovered thousands of single nucleotide polymorphism (SNP) loci that are associated with complex traits. However, the majority of GWAS discoveries are located in non-coding regions and the biological mechanisms behind these associations are not well understood. Transcriptome-wide association studies (TWAS) have gained popularity in recent years by generating biological interpretable discoveries and facilitating the identification of novel associations that have been missed by GWAS. TWAS has identified more than hundreds of susceptibility genes for many complex diseases and traits, including cancers. Here, in this review, we first summarize TWAS methods, then discuss the opportunities for cancer studies and finally review current challenges and future directions for this method.
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